bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on cellular events in post-thymectomy autoimmune oophoritis in mice. II. Requirement of Lyt-1 cells in normal female mice for the prevention of oophoritis.
Authors: Sakaguchi S , Takahashi T , Nishizuka Y
Published: June 2004

Autoimmune oophoritis that develops in A/J mice after neonatally thymectomy (NTx) was prevented by a single intraperitoneal injection of spleen cells or thymocytes from normal adult female mice. Prevention of oophoritis was achieved when spleen cells were given within 2 wk after Tx. When spleen cells were obtained from neonatally oophorectomized mice, four times more cells were required for the prevention of oophoritis, but those from the mice oophorectomized on day 7 after birth had equivalent capacity to prevent oophoritis to those from normal female mice. The spleen cells from normal A/J mice that prevented the development of oophoritis in NTx A/J mice were Thy-1+, Lyt-1+,23-, Ia-, Qa-1-, sensitive to in vitro irradiation with 400 rad, resistant to administration of cyclophosphamide or anti-thymocyte serum, and were not eliminated by adult thymectomy. Thymocytes with oophoritis-preventing capacity were also found to be Lyt-1+,23- and TL-1,2,3-. These results seem to correlate well with the finding that the Lyt-1 subpopulation is substantially decreased in NTx mice. The results suggest that, in this post-thymectomy autoimmune oophoritis, NTx abrogates the Lyt-1 T cell subpopulation that serves as suppressive or regulatory cells over developing self-reactive cells directed toward ovarian antigens, and eventually may cause autoimmune oophoritis.
Cytotoxic T lymphocyte responses in allogeneic radiation bone marrow chimeras. The chimeric host strictly dictates the self-repertoire of Ia-restricted T cells but not H-2K/D-restricted T cells.
Authors: Bradley S M , Kruisbeek A M , Singer A
Published: June 2004

The present report has used fully H-2 allogeneic radiation bone marrow chimeras to assess the role of host restriction elements in determining the self-specificity of Ia- and H-2K/D-restricted T cells that participate in the generation of trinitrophenyl (TNP)-specific cytotoxic T lymphocytes (CTL). It was demonstrated that there exists a stringent requirement for the recognition of host thymic-type Ia determinants, but there exists only a preference for host thymic-type H-2K/D determinants. Indeed, once the stringent requirement for recognition of host Ia determinants was fulfilled, anti-TNP CTL were generated in response to TNP-modified stimulators that expressed either donor-type or host-type H-2K/D determinants. The CTL that were generated in response to TNP-modified donor-type stimulators were shown to be specific for TNP and restricted to the non-thymic H-2K/D determinants of the chimeric donor. Thus, these results demonstrate in a single immune response that the thymic hypothesis accurately predicts the self-specificity expressed by Ia-restricted T cells, but does not fully account for the self-specificity expressed by H-2K/D-restricted T cells. These results are consistent with the concept that H-2K/D-restricted T cells, but not Ia-restricted T cells, can differentiate into functional competence either intrathymically or extra-thymically. The present results are also informative for understanding the cellular interactions that are required for the generation of antigen-specific CTL responses. The Ia-restricted T cells that are required for the generation of H-2K/D-restricted anti-TNP CTL were shown to be helper T (TH) cells since (a) like TH cells functioning in antibody responses, they were specific for Ia determinants expressed by accessory cells, and (b) their function could be replaced by either TNP-primed, irradiated TH cells or by nonspecific soluble helper factors. It was also shown that the T-T cell interaction between Ia-restricted TH cells and H-2K/D-restricted precursor CTL (pCTL) is not Ia restricted. Rather, the results demonstrate that the generation of anti-TNP CTL responses involve two parallel sets of major histocompatibility complex-restricted cell interactions, an Ia-restricted TH-accessory cell interaction required for TH cell activation, and an H-2K/D-restricted pCTL-stimulator cell interaction required for pCTL stimulation. The interaction between activated TH cells and stimulated pCTL is mediated, at least in part, by nonspecific soluble helper factors.
Induction of Ia antigen in rat epidermal cells and gut epithelium by immunological stimuli.
Authors: Barclay A N , Mason D W
Published: June 2004

The expression of Ia antigen in rat keratinocytes and gut epithelium was found to be inducible by a variety of immunological stimuli. Graft-vs.-host disease (GvHD) was accompanied by the appearance of Ia antigen in both sites, whereas local immunological stimuli, such as a contact-sensitizing agent applied to the skin and Trichinella spiralis infection of the gut, caused the expression of Ia antigen confined to the sites of contact of these stimuli with the tissues involved. Both T helper and T cytotoxic/suppressor subsets of parental lymphocytes, used to produce GvHD in F1 hybrid recipients, induce Ia expression in the skin and gut of these hosts, but simultaneous removal of both subsets from the donor inocula prevented induction. The Ia antigen expression associated with GvHD was shown to be of host origin but was not acquired from bone marrow-derived cells. Attempts to detect Ia antigen in serum or lymph of rats with GvHD gave negative results, and it was shown that Ia+ cells in the lamina propria of the small intestine did not take up detectable amounts of Ia antigen from the Ia+ intestinal epithelium. It appears that the local recognition of antigen by T lymphocytes can result in the induction of Ia antigen in keratinocytes and in the epithelial cells of the intestine. This antigen is synthesized by the cells in which it is found, and the observation that immunological stimuli are responsible for its appearance suggests that its role is an immunological one. Failure to find evidence that the gut epithelium Ia antigen was transferred to lymph or taken up by other Ia+ cells in the intestinal villi supports the view that this Ia (and, by analogy, that found in keratinocytes) serves a local function, and the possibility that it is involved in antigen presentation to T cells is discussed.
Leukocyte subpopulations elicited by a nontumorigenic variant of B16 melanoma: their role in direct rejection of the melanoma and in prevention of tumorigenesis in Winn assays.
Authors: Calvelli T A , Freedman V H , Silverstein S C , Silagi S
Published: June 2004

The mechanisms by which various leukocyte subpopulations elicited by an immunogenic, nontumorigenic subclone (C3471) of B16 melanoma caused rejection of the tumorigenic parental melanoma (B559), were investigated. Leukocytes from C3471-immune mice were co-injected with B559 tumor cells in Winn assays into normal syngeneic recipients. Tumor formation by B559 cells was prevented when C3471-immune (a) unfractionated peritoneal leukocytes, or (b) glass-adherent peritoneal cells (90% macrophages), or (c) nylon wool purified nonadherent cells (95% Thy-1.2+) were used in the Winn assays. If the C3471-immunized mice were treated with antithymocyte serum before harvest of their peritoneal cells, none of these leukocyte populations were effective in the Winn assay. However, macrophages from these immunologically compromised donors regained their tumoricidal activity after incubation in vitro with T lymphocytes from untreated C3471-immune donors; similarly, C3471-immune lymphocytes rendered normal resident peritoneal macrophages tumoricidal in Winn assays. When C3471-immunized mice were irradiated or treated with antithymocyte serum before direct challenge with B559 cells, melanomas developed, thus providing additional evidence for the need for intact T cell function to establish immunity against the melanoma. Furthermore, when Winn assay recipients were treated with antithymocyte serum, neither C3471-immune macrophages nor T cells were able to prevent tumor formation. These findings indicate that antithymocyte serum-sensitive (Thy-1.2+) lymphocytes are necessary both for the generation of tumoricidal leukocytes in C3471-immunized mice, and for the rejection of B559 melanoma by demonstrably tumoricidal macrophages in Winn assay recipients. In addition, long-lasting immunity developed in 50% of the normal mice that had received both C3471-immune peritoneal cells and B559 tumor cells, as manifested by their capacity to reject a second challenge with B559 cells 40-60 d later.
Immunogenicity of retransplanted rat kidney allografts. Effect of inducing chimerism in the first recipient and quantitative studies on immunosuppression of the second recipient.
Authors: Lechler R I , Batchelor J R
Published: June 2004

It has been previously shown that long surviving, enhanced (AS X AUG)F1 rat kidneys residing in a primary AS recipient are not acutely rejected if transferred into a second AS recipient. The reduced immunogenicity of the retransplanted graft was attributed to a depletion of incompatible passenger cells. It is shown here that if the primary AS recipient is made chimeric by x irradiation and injection of (AS X AUG)F1 bone marrow cells, transfer of the long surviving, enhanced graft into a second AS recipient provokes acute graft rejection comparable to that observed when normal (AS X AUG)F1 kidneys are transplanted into untreated AS recipients. Transplantation of passenger cell-depleted AUG kidneys into AS recipients leads to graft rejection, with a median survival time of 22 d. Treatment of these recipients with as little as 1.5 mg/kg cyclophosphamide for 14 d induces prolonged graft survival. By contrast, five times as much cyclophosphamide treatment is required to induce prolonged survival of normal AUG kidneys (i.e., containing incompatible passenger cells) transplanted to AS recipients. These results confirm that the major alloimmunogenic stimulus of rat kidney grafts is provided by the incompatible passenger cells.
Selection of restriction specificities of virus-specific cytotoxic T cells in the thymus: no evidence for a crucial role of antigen-presenting cells.
Authors: Zinkernagel R M
Published: June 2004

The proposal was tested that (P1 X P2) F1 leads to P1 irradiation bone marrow chimeras expressed predominantly P1-restricted T cells because donor derived stem cells were exposed to recipient derived antigen-presenting cells in the thymus. Because P1 recipient-derived antigen-presenting cells are replaced only slowly after 6-8 wk by (P1 X P2) donor-derived antigen-presenting cells in the thymus and because replenished pools of mature T cells may by then prevent substantial numbers of P2-restricted T cells to be generated, a large portion of thymus cells and mature T cells were eliminated using the following treatments of 12-20-wk-old (P1 X P2) F1 leads to P1 irradiation bone marrow chimeras: (a) cortisone plus antilymphocyte serum, (b) Cytoxan, (c) three doses of sublethal irradiation (300 rad) 2d apart, and (d) lethal irradiation (850 rad) and reconstitution with T cell-depleted (P1 X P2) F1 stem cells. 12-20 wk after this second treatment, (P1 X P2) leads to P1 chimeras were infected with vaccinia-virus. Virus-specific cytotoxic T cell reactivity was expressed by chimeric T cells of (P1 X P[2) F1 origin and was restricted predominantly to P1. Virus-specific cytotoxic T cells, therefore, do not seem to be selected to measurable extent by the immigrating donor-derived antigen-presenting cells in the thymus; their selection depends apparently from the recipient-derived radioresistant thymus cells.
Purification and characterization of fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA).
Authors: Hokland P , Rosenthal P , Griffin J D , Nadler L M , Daley J , Hokland M , Schlossman S F , Ritz J
Published: June 2004

Fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA) were purified from both fetal liver and fetal bone marrow by immune rosetting with sheep erythrocytes coated with rabbit anti-mouse immunoglobulin and by fluorescence-activated cell sorting. Dual fluorescence techniques disclosed that these cells were heterogenous with respect to the expression of a series of differentiation and activation antigens defined by monoclonal antibodies. Thus, whereas all CALLA+ cells were Ia+ and expressed two activation antigens, J2 and T10, only 30-50% expressed B1 antigen. Furthermore, using methanol-fixed cells, it could be shown that approximately 20% contained intracytoplasmic mu chains (cyto-mu) and that approximately 15% were positive for the terminal transferase enzyme (TdT) marker. The CALLA+ fetal cells thus closely resemble the childhood acute lymphoblastic leukemia cell with respect to surface marker phenotype. A population of CALLA- cells devoid of mature erythroid and myeloid surface markers was found to contain higher numbers of TdT+ cells but lower numbers of cyto-mu, B1, and Ia+ cells than the CALLA+ subset. In vitro analysis of normal, purified CALLA+ cells demonstrated that incubation at 37 degrees C with J5 monoclonal antibody specific for CALLA resulted in the specific modulation of surface antigen. Similar results have previously been obtained with CALLA+ tumor cells. Although phenotypic analysis of CALLA+ cells suggests that these cells are relatively immature lymphoid cells, CALLA+ cells do not appear to contain either myeloid precursor cells (CFU-G/M) or the earliest lymphoid stem cells.
Stages of renal ontogenesis identified by monoclonal antibodies reactive with lymphohemopoietic differentiation antigens.
Authors: Platt J L , LeBien T W , Michael A F
Published: June 2004

Differentiation antigens of T and B lymphocytes were sought in human fetal and adult kidney tissues with monoclonal antibodies by indirect immunofluorescence. Antibodies that identify B cells (BA-1 and anti-B1) and leukemia-associated antigens (BA-2, BA-3, and J5) reacted with renal glomerular and tubular epithelium at characteristic stages of nephron development. BA-1 and BA-2 identified primitive epithelium of the glomerulus, and ureteral bud and nephron development was characterized by loss of BA-1 and BA-2 binding by visceral glomerular and proximal tubular epithelium. In contrast, J5 and BA-3 did not react with primitive epithelium but identified visceral and proximal tubular epithelium after appearance of the glomerular basement membrane and throughout subsequent nephron differentiation. Anti-B1 reacted with ureteral bud and distal nephron epithelium in more mature fetal tissues. Monoclonal antibodies that identify populations of T cells and thymocytes did not react with parenchymal cells of fetal or adult kidneys. They did identify interstitial mononuclear cells whose size and relative numbers appeared gestationally related. Monoclonal antibodies that recognize a human monomorphic HLA-DR determinant reacted with glomerular and peritubular capillaries as early as 11 wk of gestation. The distribution and density of HLA-DR expression appeared more related to gestation than nephron development. The relationship between renal parenchymal expression of lymphohemopoietic antigens and glomerular acquisition of C3b receptor activity was determined using C3b-coated fluoresceinated Escherichia coli. In fetal tissues, C3b receptor activity appeared developmentally related to the loss of determinants recognized by BA-1 and BA-2 and to the appearance of J5 and BA-3 reactivity with visceral glomerular epithelium. Tissue binding and comparative avidity of J5 and BA-3 antibodies was studied in a series of experiments, the results of which suggest that these antibodies are directed against the same epitope or closely related epitopes of the common acute lymphoblastic leukemia antigen. The common expression of differentiation antigens and C3b receptors by cells of lymphohemopoietic lineage and renal epithelia suggests the possibility of heretofore unrecognized commonality of function or developmental experience.
Anti-cell surface pemphigus autoantibody stimulates plasminogen activator activity of human epidermal cells. A mechanism for the loss of epidermal cohesion and blister formation.
Authors: Hashimoto K , Shafran K M , Webber P S , Lazarus G S , Singer K H
Published: June 2004

Binding of anti-cell surface pemphigus autoantibodies to cultured human epidermal cells stimulates synthesis and secretion of plasminogen activator (PA). Increases in PA activity were detected within 6 h of the addition of IgG and stimulation was dependent upon IgG concentration. Stimulation of PA activity was inhibited by cycloheximide, which indicates that synthesis of protein was necessary. Pharmacological doses of dexamethasone also prevented IgG-induced stimulation of PA. Electrophoretic profiles of PA secreted by cultured human epidermal cells in the presence or absence of pemphigus IgG were similar. The majority of the PA activity comigrated with the higher-molecular-weight species of human urokinase (approximately 55,000). Explants of normal human skin incubated with pemphigus vulgaris IgG displayed loss of epidermal cohesion similar to that observed in patient biopsies. The histologic changes were potentiated by the inclusion of human plasminogen. Loss of epidermal cohesion in normal skin explants incubated with pemphigus foliaceous IgG was dependent upon the addition of plasminogen and was inhibited by aprotinin or lima bean trypsin inhibitor, which indicated that plasmin is the active enzyme in producing acantholysis. These data support the hypothesis that stimulation of PA by the anti-cell surface autoantibodies of pemphigus results in a localized increase in plasmin, which through proteolysis produces the loss of epidermal cohesion characteristic of pemphigus.
Possible role for C-reactive protein in the human natural killer cell response.
Authors: Baum L L , James K K , Glaviano R R , Gewurz H
Published: June 2004

Functional NK activity can be removed from human PBL and from phagocyte- and T cell-depleted LGL preparations by treatment with antisera specific for C-reactive protein (CRP) in the presence of complement (C). Pretreatment of NK effector cells with high concentrations of anti-CRP in the absence of C also depletes functional activity. These results indicate that CRP or an antigenically similar molecule is present on a population of NK effector cells. Fluorescent antibody studies in which biotin-avidin amplification was used confirm the presence of surface CRP (S-CRP) on a small percentage of nonphagocytic peripheral blood mononuclear cells. S-CRP readily caps off, which suggest that removal by capping obviates killing by this cell population. This indicates that S-CRP or a molecule that co-caps with S-CRP may be required for successful effector-target cell interaction. The addition of exogenous CRP or CRP-CPS complexes, however, does not alter NK responses. A subpopulation of lymphoid cells responsible for functional NK activity therefore appears to bear surface CRP.
IgE class-restricted tolerance induced by neonatal administration of soluble or cell-bound IgE.
Authors: Chen S S , Katz D H
Published: June 2004

Induction of IgE class-restricted tolerance was studied in high IgE-responder (BALB/c X SJL)F1 mice, of which the parental BALB/c and SJL mice are high and low IgE-responder mice, respectively. 2,4-Dinitrophenyl (DNP)-specific monoclonal IgE was administered to (BALB/c X SJL)F1 mice neonatally in two forms: soluble IgE at 250 micrograms per injection, or 10-100 ng of IgE coupled to 25-50 X 10(6) syngeneic splenocytes by binding to the chemically reactive hapten trinitrobenzene sulfonate (TNBS) or directly conjugated via a heterobifunctional reagent, N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP). Polyclonal induction of IgE class-restricted tolerance was observed in (BALB/c X SJL)F1 mice, neonatally treated with soluble IgE or IgE-conjugated syngeneic splenocytes. Thus these mice failed to mount IgE antibody responses to either keyhole limpet hemocyanin or ovalbumin challenge, assessed by the passive cutaneous anaphylaxis reaction. The IgG antibody responses to these same antigens, however, were not affected by this treatment. The IgE class-restricted tolerance induced by both forms of IgE persisted up to at least 6 mo with repeated antigenic challenges. IgE coupled to syngeneic cells by TNBS or the SPDP method induced prolonged tolerance up to 9 mo. The induction of polyclonal IgE class-restricted tolerance was achieved only by monoclonal IgE, whereas DNP-specific monoclonal IgG1 plus IgG2b coupled to syngeneic splenocytes by the SPDP method failed to modulate either IgE or IgG antibody responses. In contrast, (BALB/c X A/J)F1 mice, of which both parental strains are high IgE responders, developed IgE class-restricted tolerance upon repeated neonatal injection of soluble IgE, but not IgE-conjugated syngeneic splenocytes, indicating that gene products of the low IgE-responder mice contributed to the effective presentation and/or recognition of epsilon heavy chain of the IgE molecules. Taken collectively, these results demonstrated that non-antigen-specific, isotype-restricted tolerance can be induced in the IgE antibody system. The differential induction of IgE class-restricted tolerance by different forms of tolerogen in the strains studied perhaps distinguishes two underlying cellular mechanisms for IgE class-restricted tolerance.
Human B cell variants immunoselected against a single Ia antigen subset have lost expression of several Ia antigen subsets.
Authors: Accolla R S
Published: June 2004

Two monoclonal antibodies, D1-12 and BT 2.2, recognizing two distinct subsets of human Ia molecules, NG1 and NG2, respectively, present in all individuals irrespective of their HLA-DR phenotype, have been used to immunoselect cell variants from the lymphoblastoid cell line Raji. Results showed that, irrespective of the monoclonal antibody used for immunoselection, the cell variants analyzed in this study had lost the expression of both D1-12-and BT 2.2-specific antigenic determinants. Moreover, the expression of antigenic determinants specific for a third family of Ia molecules, the DC-1 subset, were also lost in the cell variants. In contrast, expression of HLA A, B, and C common structures, as recognized by the W6.32 monoclonal antibody, as well as expression of surface immunoglobulins, were not affected. Possible mechanisms inducing such a coordinate loss of expression of several families of human Ia molecules are discussed.
Polymorphonuclear neutrophils express the common acute lymphoblastic leukemia antigen.
Authors: Cossman J , Neckers L M , Leonard W J , Greene W C
Published: June 2004

Monoclonal antibodies J5, VIL-A1, and BA-3, known to react with the common acute lymphoblastic leukemia antigen (CALLA) were found to specifically stain normal human polymorphonuclear neutrophils (PMN). The antigen detected on PMN had a molecular weight (95,000-110,000 mol wt) close to that of CALLA (95,000-100,000 mol wt) and thus these surface membrane antigens are likely related, if not identical. The fluorescent staining intensity of PMN is comparable to that of CALLA-positive leukemic cells and the presence of PMN in patient samples could potentially produce false-positive results in diagnosis.
The activity of natural cytotoxic cells is augmented by interleukin 2 and interleukin 3.
Authors: Lattime E C , Pecoraro G A , Stutman O
Published: June 2004

Murine natural killer (NK) and natural cytotoxic (NC) cells showed different patterns of augmentation of lytic activity after preincubation for 24 h with either poly-IC, interleukin 2 (IL-2), or interleukin 3 (IL-3): (a) Poly-IC augmented only NK cells, with no effect on NC activity, as we have previously observed (4); (b) IL-2 augmented both NK and NC activity; and (c) IL-3 augmented only NC lysis, without affecting NK activity. In addition, both precursor and the augmented effector cells showed differences in expression of the Qa-5 surface marker: NK precursors and effectors are Qa 5+, whereas NC precursors and effector cells are Qa-5-.
T cells produce an antigen-binding factor with in vivo activity analogous to IgE antibody.
Authors: Askenase P W , Rosenstein R W , Ptak W
Published: June 2004

T cell-dependent activation of resident tissue mast cells is required for the elicitation of delayed-type hypersensitivity skin reactions in mice. A T cell-derived antigen-binding factor that transfers the ability to elicit an immediate hypersensitivity-like skin reaction is described and compared with a hybridoma IgE antibody. Both the T cell factor and IgE mediate reactions with increased vascular permeability and both are mast cell dependent, as they are inactive in two different types of mast cell deficient mice (W/Wv and Sl/Sld). The T cell factor was distinguished from IgE by affinity chromatography using specific anti-IgE and anti-factor antibodies and by a shorter duration of passive sensitization. The T cell factor is a suitable candidate for participation in the mechanism by which T cells activate mast cells in delayed-type hypersensitivity.
Monoclonal antibody against human T cell leukemia virus p19 defines a human thymic epithelial antigen acquired during ontogeny.
Authors: Haynes B F , Robert-Guroff M , Metzgar R S , Franchini G , Kalyanaraman V S , Palker T J , Gallo R C
Published: June 2004

Using monoclonal antibody 12/1-2 against a 19,000-dalton human T cell leukemia virus (HTLV) protein (anti-p19), previously demonstrated to be reactive with HTLV-infected human cells, but not in numerous other uninfected cells, we found a reactive antigen to be expressed on the neuroendocrine component of human thymic epithelial cells but not on any other normal epithelial or neuroendocrine human tissues. Moreover, this reactive antigen is acquired on neuroendocrine thymic epithelium during thymic ontogeny--first appearing on fetal thymic epithelial cells between 8 and 15 wk gestation. While only a portion of thymic epithelial cells in the subcapsular cortical region of 15- and 24-wk fetal thymuses contained anti-p19+ epithelial cells, the entire subcapsular cortical region of newborn thymus epithelium was anti-p19+. By age 3 yr, normal subjects' entire subcapsular cortical and medullary thymic epithelium was anti-p19+. Using antibody against HTLV core protein, p24, and c-DNA probes for HTLV DNA, neither HTLV-specific p24 protein nor proviral DNA could be demonstrated in anti-p19+ thymic epithelial tissue. However, thymic epithelial extracts, disrupted HTLV extracts, as well as purified HTLV p19 antigen all inhibited the binding of anti-p19 antibody to thymic epithelium. Thus, anti-p19 may recognize a determinant on an HTLV-encoded 19,000-dalton structural protein that is shared by human thymic epithelium. Alternatively, anti-p19 defines a host encoded protein that is selectively expressed by normal thymic epithelium, and is induced to be expressed in HTLV-infected malignant T cells.
Surface alterations of erythrocytes in Plasmodium falciparum malaria. Antigenic variation, antigenic diversity, and the role of the spleen.
Authors: Hommel M , David P H , Oligino L D
Published: June 2004

The surface of erythrocytes infected with late developmental stages of Plasmodium falciparum is profoundly altered and new antigenic determinants can be detected by surface immunofluorescence using immune squirrel monkey serum. The expression of these parasite-specific antigenic determinants on the surface of the host erythrocyte can be modulated by the presence or absence of the spleen and by immune pressure. An antigenic switch occurred when a cloned population of the Ugandan Palo Alto strain of P. falciparum was transferred from a splenectomized into an intact monkey and this switch was reversible. In another strain (Indochina-1), we showed that the parasites isolated during secondary and recrudescent peaks expressed erythrocyte-associated surface antigens different from the parasites isolated during the primary infection; six variant antigenic types distinct from the original population were isolated in this way. The passive transfer of immune serum can induce antigenic variation and this can occur in a cloned parasite. The various mechanisms of antigenic variation in P. falciparum are discussed in the context of strain-specific diversity and the role of antigenic diversity in acquired immunity.
Genetic and temporal control of neonatal antibody expression.
Authors: Denis K A , Klinman N R
Published: June 2004

Two hybridoma cell lines were established with B cells derived from neonatal BALB/c spleen cells. The anti-dinitrophenyl (DNP) antibodies derived from these lines were characterized with respect to their isotype, affinity, and isoelectric point. Antiidiotypic reagents were prepared that permit an analysis of the representation of antibodies sharing idiotype with these two hybridomas in the developing and mature B cell pool of BALB/c mice (Igha) and other murine strains. One of the two antibodies, TF2-36, was found to be indistinguishable from 14% of anti-DNP monoclonal antibodies derived in fragment culture from spleen cells of 1-4-d-old BALB/c donors. B cells expressing this idiotype were found to represent approximately 2% of the anti-DNP-specific repertoire after the 1st wk of neonatal development and into adulthood. The second hybridoma antibody, TF2-76, was found to be expressed at very low levels during the first several days of neonatal development; however, B cells expressing this idiotype increased in frequency during the 2nd wk of neonatal development representing 7% of all DNP-responsive B cells 12-13 d after birth. The proportion of B cells expressing this idiotype also decreased to approximately 2% in adults. The relatively late appearance of B cells bearing this idiotype was confirmed by their susceptibility to tolerance induction after the 1st wk of neonatal development. Both the early neonatal clonotype, TF2-36, and the late neonatal antibody clonotype, TF2-76, were found to be expressed in a similar fashion in F1 mice constructed between Igha and Ighb parentals, but both were expressed at very low levels during the development of Ighb mice. Thus, the control of the magnitude of expression of these neonatal clonotypes appears to be associated with the Igh locus.
Antigen responsiveness of the mature and generative B cell populations of aged mice.
Authors: Zharhary D , Klinman N R
Published: June 2004

The deficit of humoral immune responsiveness associated with aging was investigated at the level of individual antigen-specific B cells. It was found that mature dinitrophenyl (DNP)-responsive B cells isolated from the spleen of aged mice gave rise to clones of antibody-forming cells that were normal with respect to both the amount and relative affinity of anti-DNP antibody produced. However, although the proportion of immunoglobulin-bearing cells in the spleen of aged mice was normal, the proportion of cells that responded to T cell dependent DNP-specific stimulation (1.1 per 10(6) injected cells) was significantly lower than the proportion that responded when cells were obtained from the spleen of young mice (2.3 per 10(6) injected cells). To examine the origin of this diminution in antigen-responsive B cells, the responsiveness of precursor cells from the B cell generative pool isolated as the surface immunoglobulin negative (sIg-) cells within the bone marrow was evaluated. The frequency of DNP-responsive cells in both intact bone marrow cell suspensions and the sIg- subpopulation was not significantly different when such cells were isolated from aged vs. young individuals. Thus, it would appear that among the immunologic deficits associated with aging is a decrease in the proportion of antigen-responsive B cells, which is associated with maturation of B cell clones in the aged environment and occurs during the migration of cells from the bone marrow to the spleen.
Haptens can serve as surrogate transplantation antigens in a manner that demonstrates H-2 restriction of graft rejection.
Authors: Streilein J W , Bergstresser P R
Published: June 2004

Hapten-immune mice are capable of rejecting syngeneic skin grafts that are derivatized with the relevant hapten, but only if the hapten is applied while the graft is "healing in." This model system was used to demonstrate that the hapten-specific immune effectors responsible for rejection are restricted by H-2 determinants of the recipient. Thus, haptens can be used in vivo as surrogate transplantation antigens for the study of immunopathogenic mechanisms in transplantation immunity.
Rearrangement of immune complexes in glomeruli leads to persistence and development of electron-dense deposits.
Authors: Mannik M , Agodoa L Y , David K A
Published: June 2004

Covalently, cross-linked immune complexes were prepared with multivalent 2-nitro-4-azidophenyl X human serum albumin (NAP X HSA) and antibodies to NAP at five times antigen excess. After purification with gel filtration, affinity chromatography with antigen-agarose column, and addition of the hapten, 9.5% of the antibodies dissociated from the complexes by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. After injection of these cross-linked immune complexes into mice, glomeruli stained for the complexes by immunofluorescence microscopy for only a few hours and electron-dense deposits were not detected. In contrast, when the same immune complexes with comparable lattice but without covalent cross-linking were administered to a second group of mice, the initial deposition by immunofluorescence was comparable and then increased to extensive deposits that persisted to 96 h. In this second group of mice extensive electron-dense deposits evolved. These observations supported the conclusion that the immune complexes initially deposited from circulation must undergo rearrangement to persist and to form electron-dense deposits in glomeruli. The covalently cross-linked immune complexes existed in glomeruli only for a short period of time since these complexes could not rearrange.
Induction of a cross-reactive idiotype dextran-positive antibody response in two IgH-Cb mouse strains treated with anti-J558 cross-reactive idiotype antibodies.
Authors: Pène J , Bekkhoucha F , Desaymard C , Zaghouani H , Stanislawski M
Published: June 2004

The effect of IdX-specific rabbit and allogeneic antiidiotype antibodies (Ab2) was investigated in vivo in Igh-Cb mouse strains with respect to the induction of a cross-reactive idiotype (IdX)-positive anti-alpha (1-3) Dextran (Dex) response. These C.B20 and C57Bl/6 mice have an allotype-linked incapacity to respond with IdX-positive anti-alpha (1-3) Dex antibodies upon conventional immunization with Dex B1355. 7 d after the rabbit Ab2 injections, IdX-positive Ig (Ab3) and IdX-positive anti-alpha (1-3) Dex antibodies (Ab1') were detected in the sera of each tested mouse. The affinity-purified Ab1' were idiotypically indistinguishable from reference BALB/c IdX-positive myeloma proteins and BALB/c anti-alpha (1-3) Dex antibodies (Ab1) in a competitive inhibition radioimmunoassay, while Ab3 Ig appeared idiotypically deficient and did not bind to Dex. The response to the alpha (1-6) linkage of Dex was not affected in these mice. A large fraction of the Ab1' and Ab3 responses of both mouse strains were of the IgG1 class. The Ab1' antibodies differed from BALB/c Ab1 by lower relative binding to five of eight tested Dex, and by expressing the Igh4b allotype determinants on the IgG1 antibodies. This study identifies the products of a VHDex gene that appears to be under regulatory control in the Ighb mice. Its association with the b haplotype suggests that this gene may differ structurally from the BALB/c VHDex gene.
Secretion of a proteolytic anticoagulant by Ancylostoma hookworms.
Authors: Hotez P J , Cerami A
Published: June 2004

Hookworms of the genus Ancylostoma secrete an anticoagulant that both inhibits the clotting of human plasma and promotes fibrin clot dissolution. This anticoagulant activity is attributable to a 36,000 dalton proteolytic enzyme. The protease can degrade fibrinogen into five smaller polypeptides that intrinsically have anticoagulating properties, covert plasminogen to a mini-plasminogen-like molecule, and hydrolyze a synthetic peptide substrate with specificity for elastolytic enzymes. It is hypothesized that the parasite uses this enzyme to prevent blood clotting while feeding on villous capillaries.
An early component of delayed-type hypersensitivity mediated by T cells and mast cells.
Authors: van Loveren H , Meade R , Askenase P W
Published: June 2004

In four different systems it was shown that murine delayed-type hypersensitivity (DTH) responses at 18-48 h were preceded by early 2-h responses. CBA mice immunized with picryl chloride, BDF1 mice immunized with oxazolone, BALB/c mice immunized with dinitrofluorobenzene, and C57BL/6 mice immunized with L5178Y lymphoma cells, and challenged with the appropriate specific antigen, all gave rise to expected 18-48 h delayed-in-time hypersensitivity reactions, but all of these responses were preceded by early hypersensitivity reactions that peaked at 2 h. These early 2-h reactions are transferable with T cells or with a T cell-derived, antigen-binding factor and are antigen-specific. The early and late components of DTH reactions are mast cell dependent since neither are elicited in mast cell deficient W/Wv or Sl/Sld mice. The T cell activity mediating the early component of DTH is demonstrable as early as 24 h after immunization, while the classical late component of DTH is not demonstrable until days 3-4. The difference in onset after immunization of the early and late components of DTH, and the different kinetics of these components in recipients of cell transfers that were challenged immediately or 24 h after transfer, led to the hypothesis that immunization for DTH leads to rapid induction in lymphoid organs of a certain population of T cells to produce an antigen-binding factor. This factor sensitizes peripheral tissues, probably mast cells, and local challenge with appropriate antigen leads to mast cell activation and release of the vasoactive amine serotonin, resulting in increased permeability of the local vasculature. This allows other circulating antigen-specific T cells, which are induced later after immunization, to enter the tissues and interact with antigen, resulting in production of chemoattractant lymphokines that recruit accessory leukocytes such as monocytes and polymorphs to enter the tissues via gaps between endothelial cells. These inflammatory cells, that are recruited to the site via two different T cell activities, constitute the characteristic infiltrate of DTH responses. Identification of an early 2-h component of DTH that is T cell- and mast cell-dependent provides evidence that the tissue-sensitizing, antigen-binding, T cell factor probably functions in vivo in the early phases of DTH responses.
Localization of the membrane attack complex (MAC) in experimental immune complex glomerulonephritis.
Authors: Koffler D , Biesecker G , Noble B , Andres G A , Martinez-Hernandez A
Published: June 2004

The role of the membrane attack complex (MAC) as a mediator of renal tissue injury was evaluated in rats affected by bovine serum albumin (BSA)-induced immune complex glomerulonephritis. Immunofluorescence studies revealed concurrent deposits of IgG, BSA, C3, and the MAC along glomerular capillary walls, although the MAC manifested a more restricted distribution than that observed for immune complexes. Immunoelectron microscopic techniques were utilized to demonstrate immune complexes, C3, and the MAC within dense deposits in the subepithelial aspect of the basement membrane. Visceral epithelial foot processes were fused in areas overlying large dense deposits and exhibited intense staining for the MAC, lesser reactivity for C3 but IgG was absent from the foot process membranes. Smaller granular deposits of immune complexes, C3, and the MAC were observed in the subendothelial region of the lamina rara interna and the lamina densa. Immune complexes may activate the classical complement pathway causing diffuse injury to the glomerular basement membrane (GBM), allowing subepithelial accumulation of complexes. These observations implicate the MAC as a mediator of GBM and juxtaposed podocyte membrane injury, thereby contributing to disruption of the glomerular filtration barrier. IgG and C3 were demonstrated within tubulointerstitial regions on the surface of collagen fibers in close proximity to the tubular basement membrane (TBM) of proximal convoluted tubules. Within the TBM, C3 localization was prominent with diminished reactivity for the MAC, but IgG was not detectable. The demonstration of C3 and scant MAC deposits in the TBM of nonimmunized control rats without evidence of interstitial IgG and C3 deposits suggests that both nonimmune and immune processes play a role in the pathogenesis of extraglomerular lesions. Evidence derived from these morphologic studies indicates that the MAC is associated with injury to the GBM, foot process membranes of visceral epithelium, and the TBM. Further experiments designed to selectively enhance or inhibit the deposition of MAC and assess consequent renal dysfunction are required to substantiate hypotheses concerning the in vivo membranolytic potential of the MAC in experimental immune complex glomerulonephritis.
Hapten-reactive inducer T cells. I. Definition of two classes of hapten-specific inducer cells.
Authors: Clayberger C , Dekruyff R H , Aisenberg J , Cantor H
Published: June 2004

Hapten-reactive inducer T cell clones can be divided into two groups based on their activation specificity. The first and largest group is conjugate specific. These clones are activated only by hapten coupled to the same carrier protein used for in vitro selection. The second group, which is quite rare, is hapten specific. Clones of this type are activated by hapten coupled to all foreign and autologus proteins tested. Both types of clones corecognize soluble antigen in association with products of the I-A locus. The hapten-specific cells were used to analyze the molecular basis of I-A vs. I-E gene control. The physiologic significance of hapten- and carrier-specific inducer T cells in the response to foreign antigens and autoantigens is discussed.
Regulation of natural antiallotype antibody responses by idiotype network-induced auto-antiidiotypic antibodies.
Authors: Rodkey L S , Adler F L
Published: June 2004

This study was designed to determine whether natural immune responses could elicit immunoregulatory auto-antiidiotypic antibodies. Female rabbits heterozygous at the a and b Ig loci were bred to homozygous males. Offspring of one such breeding were studied for natural production of antibodies specific for the noninherited allotypes and for the production of immunoregulatory auto-antiidiotypic antibodies. All offspring mounted natural antiallotype responses. The anti-a1 responses cycled as a function of time whereas the anti-b5 responses were invariant. Anti-a1 responses from two offspring were shown to change specificity for different a1 subsets as they cycled. Anti-a1 was purified from the first cycle and was used to assay for auto-antiidiotypic responses. Auto-antiidiotypic antibodies were detected and were found to cycle in an inverse way with the anti-a1 cycles. The idiotopes detected using the natural auto-antiidiotypic antisera were strongly cross-reactive. Subsequent deliberate immunization showed that antibodies specific for all a1 subsets could be elicited after auto-antiidiotypic regulation had functioned. The data support the interpretation that idiotype network interactions indeed function in naturally occurring immunologic situations and are not merely laboratory curiosities or artifacts.
Treponema pallidum receptor binding proteins interact with fibronectin.
Authors: Peterson K M , Baseman J B , Alderete J F
Published: June 2004

Analysis of plasma proteins avidly bound to T. pallidum surfaces revealed the ability of T. pallidum to acquire numerous host macromolecules. No acquisition was evident by the avirulent spirochete, T. phagedenis biotype Reiter. Western blotting technology using hyperimmune antifibronectin serum as a probe revealed the ability of virulent treponemes to avidly bind fibronectin from a complex medium such as plasma. The specificity of the tiplike adherence of motile T. pallidum to fibronectin-coated glass surfaces and to fibronectin on HEp-2 cells was reinforced by the observation that pretreatment of coverslips or cell monolayers with monospecific antiserum against fibronectin substantially reduced T. pallidum attachment. The stoichiometric binding of T. pallidum to fibronectin-coated coverslips and the inability of unlabeled or 35S-radiolabeled treponemes to interact with glass surfaces treated with other plasma proteins further established the specific nature of the interaction between virulent T. pallidum and fibronectin. The avid association between three outer envelope proteins of T. pallidum and fibronectin was also demonstrated. These treponemal surface proteins have been previously identified as putative receptor-binding proteins responsible for T. pallidum parasitism of host cells. The data suggest that surface fibronectin mediates tip-oriented attachment of T. pallidum to host cells via a receptor-ligand mechanism of recognition.
Ia antigens in rat kidney, with special reference to their expression in tubular epithelium.
Authors: Mayrhofer G , Schon-Hegrad M A
Published: June 2004

The distribution of Ia antigens in rat kidneys has been investigated by an immunoperoxidase technique, using monoclonal antibodies directed at framework determinants on molecules equivalent to gene products of the I-A and I-E/C regions of the mouse major histocompatibility complex (MHC). Antigens mapping to both loci were detected in proximal convoluted tubule epithelium and on scattered dendritic cells in the interstitial connective tissues, glomeruli, and mucosa of the renal pelvis. All other structures were negative. Genetic studies indicate that the levels of expression of Ia molecules from both genetic loci are controlled by non-MHC genes in epithelium, but not on lymphocytes. The subcellular distribution of Ia molecules has been investigated in tubular epithelium and is discussed in relation to their possible functions in epithelia.
A mouse gene on chromosome 5 that restricts infectivity of mink cell focus-forming recombinant murine leukemia viruses.
Authors: Hartley J W , Yetter R A , Morse H C
Published: June 2004

DBA/1, DBA/2, CBA/N, and CBA/Ca mice carry a gene which specifically restricts infectivity of mink cell focus-forming (MCF) murine leukemia viruses. The gene, designated Rmcfr, is dominant or semidominant and maps to chromosome 5; it is closely linked to the morphologic marker gene Hm. The Rmcf gene may be of much use as a means of determining the role of MCF viruses in various forms of leukemogenesis.
Antibodies to normal human melanocytes in vitiligo.
Authors: Naughton G K , Eisinger M , Bystryn J C
Published: June 2004

Most patients with active vitiligo (82% of 61) have antibodies to antigens of normal human melanocytes that can be detected by specific immunoprecipitation of radioiodinated, detergent-soluble, melanocyte macromolecules. Such antibodies were present in only 12% of patients with melanoma and in none of 35 patients with nonpigmentary skin diseases. The antibodies were directed to a common antigen(s) on melanocytes that was not present on normal fibroblasts or keratinocytes. These observations suggest that vitiligo is an autoimmune disease mediated by antibodies to melanocyte-associated antigen(s).
Metabolism of formycin B by Leishmania amastigotes in vitro. Comparative metabolism in infected and uninfected human macrophages.
Authors: Berman J D , Rainey P , Santi D V
Published: June 2004

Formycin B is metabolized by cutaneous Leishmania amastigotes within cultured human macrophages to give formycin B 5'-monophosphate and formycin A 5'-mono-, di-, and triphosphates. Formycin A is also incorporated into RNA. The activity of formycin B against amastigotes was correlated with the levels of formycin A metabolites formed in the parasites. Uninfected macrophages also convert formycin B into the same products, but the levels are markedly lower than those seen in infected macrophages. The results suggest that a sufficient therapeutic index exists to warrant consideration of formycin B as an anti-leishmanial drug in humans.