bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of an idiotypic marker of a major regulatory T cell of the immune response in B10.BR mice to ferredoxin. The relationship of idiotypic regulation to conventional hapten-carrier effects.
Authors: Weaver M , Singhai R , Sikora L , Levy J G
Published: June 2004

An anti-idiotypic antiserum was raised in rabbits to a monoclonal antibody (Fd-1) with specificity for one (the N epitope) of the two antigenic epitopes found on the ferredoxin (Fd) molecule. The anti-idiotypic antiserum (anti-Fd-1) was used to demonstrate that the Fd-1 idiotype was expressed at significant levels in most anti-Fd antisera raised in B10.BR mice. Examination of antisera raised in other mouse strains demonstrated that expression of this idiotype mapped to the IgH gene complex and was found in the antisera of all mouse strains examined with the Ig-1 allotype. When splenocytes from Fd-immune B10.Br mice were treated with anti-Fd-1 and transferred to irradiated syngeneic recipients, the adoptive secondary response was significantly higher in animals receiving treated cells as opposed to control animals, which received normal rabbit serum-treated cells. This response produced a net increase in antibody to both determinants, and the relative amount of Fd-1 idiotype was not significantly altered. Further studies with separated cell populations showed that the overall increase of anti-Fd antibody produced was attributable to the effects of the anti-idiotypic serum on a population(s) of T cells. Treatment of mice with the Fd-1 monoclonal antibody (which should react with anti-idiotypic cells) had an analogous effect to that of the anti-idiotype, in that mice so treated produced higher concentrations of anti-Fd antibodies when they were immunized and these antibodies exhibited net increases to both determinants. A model is presented to explain these results.
The export of immunoglobulin D by human neoplastic B lymphocytes.
Authors: Stevenson F K , Stevenson G T , Tutt A L
Published: June 2004

An investigation has been made into the ability of human neoplastic B lymphocytes expressing surface IgM and IgD to export IgD in culture. Cells that expressed surface Ig of the lambda light chain type frequently exported IgD (10/12 patients), whereas cells expressing surface Ig of the kappa light chain type exported no IgD, although most (8/11 patients) were able to export IgM. It appears, therefore, that in most of the 23 cases studied, cells synthesizing IgD with lambda light chains can both express and export IgD, whereas those synthesizing IgD kappa can only insert it into the surface membrane. This finding and the known preponderance of lambda in plasma IgD imply that the possession of a lambda chain facilitates the IgD secretory pathway, a conclusion that implicates a control mechanism subsequent to the surface/secretory dichotomy arising from different splicings of heavy chain messenger RNA.
Long-term growth of lines of murine dinitrophenyl-specific B lymphocytes in vitro.
Authors: Aldo-Benson M , Scheiderer L
Published: June 2004

Studies of cellular events associated with antigen-induced triggering and differentiation of B cells would be greatly facilitated by the availability of homogeneous cell lines of antigen-specific lymphocytes that can be maintained in long-term culture. By combining the techniques of enrichment of lymphocytes for antigen-specific cells, cloning in soft agar, and long-term propagation of B cells we have been able to isolate, propagate, and maintain two lines of dinitrophenyl (DNP) -specific B lymphocytes. These cell lines are B lymphocytes that have 70% and greater than 80% DNP-specific rosette-forming cells, respectively. Both cell lines secrete small amounts of antibody spontaneously but can be stimulated by antigen in vitro in the presence of either supernatants from phytohemagglutinin-stimulated spleen cells or irradiated normal filler cells. Thus far these lines have been maintained in vitro for greater than 9 mo. They will be useful in studying factors associated with B cell response.
Modulation of Tthy alloantigen expression in the neonatal mouse. The Tthy-bearing thymocyte is a precursor for the peripheral cells expressing Tind and Tsu.
Authors: Keesee S K , Owen F L
Published: June 2004

The T cell alloantigen Tthyd appears on a subpopulation of thymocytes in mice bearing the Igh-1d or e heavy chain haplotype. Ontogenetic studies have suggested that this antigen precedes the appearance of two other T cell alloantigens in the same linkage group, Tindd and Tsud. The purpose of this study was to determine if the Tthy-bearing cell is a precursor for cells in the periphery expressing Tind and Tsu. CAL-20 mice were treated at 48-h intervals beginning on the day of birth with a monoclonal antibody recognizing Tthy. Tthy alloantigen expression, monitored by cytotoxicity assays, was found to be significantly depressed in the thymuses of treated animals; Tind and Tsu also failed to appear in the periphery. Treatment with anti-Tthy caused no significant changes in frequency or surface intensity in the expression of surface Ig. Thy-1.2, Thy-1.2, and Lyt-2.2, as studied by cytofluorograph analysis. We conclude that the T-thyd-bearing cells in the thymus represent a subpopulation that may be a precursor for Tindd- and Tsud-bearing cells. However, Tthyd-bearing cells are more mature than the Thy-1.2 common T cell precursor, pre-T.
Tpre, a new alloantigen encoded in the IgT-C region of chromosome 12, is expressed on bone marrow of nude mice, fetal T cell hybrids, and fetal thymus.
Authors: Owen F L
Published: June 2004

A new T cell alloantigen, Tpre, has been identified by monoclonal F.6.9.1 antibody. This antigen is encoded by a gene linked to the cluster of T cell antigens in the IgT-C region of chromosome 12 (Tthy, Tind, and Tsu). Tpre is distinct from Tthy, Tind, or Tsu because it is expressed on bone marrow cells of the AKR nustr/nustr, the thymus repopulating precursor cell in normal adult marrow, and normal fetal thymocytes. Several fetal and adult T cell hybrids express these antigens independently. Tpre and Tthy are expressed on largely overlapping cell populations in adult thymus.
Major histocompatibility complex-restricted self-recognition in responses to trinitrophenyl-Ficoll. A novel cell interaction pathway requiring self-recognition of accessory cell H-2 determinants by both T cells and B cells.
Authors: Hodes R J , Hathcock K S , Singer A
Published: June 2004

In vitro primary antibody responses to limiting concentrations of trinitrophenyl (TNP)-Ficoll were shown to be T cell dependent, requiring the cooperation of T helper (TH) cells, B cells, and accessory cells. Under these conditions, TH cells derived from long-term radiation bone marrow chimeras were major histocompatibility complex (MHC) restricted in their ability to cooperate with accessory cells expressing host-type MHC determinants. The requirement for MHC-restricted self-recognition by TNP-Ficoll-reactive B cells was assessed under these T-dependent conditions. In the presence of competent TH cells, chimeric B cells were found to be MHC restricted, cooperating only with accessory cells that expressed host-type MHC products. In contrast, the soluble products of certain monoclonal T cell lines were able to directly activate B cells in response to TNP-Ficoll, bypassing any requirement for MHC-restricted self-recognition. These findings demonstrate the existence of a novel cell interaction pathway in which B cells as well as TH cells are each required to recognize self-MHC determinants on accessory cells, but are not required to recognize each other. They further demonstrate that the requirement for self-recognition by B cells may be bypassed in certain T-dependent activation pathways.
Experimental autoimmune thyroiditis. In vitro cytotoxic effects of T lymphocytes on thyroid monolayers.
Authors: Creemers P , Rose N R , Kong Y M
Published: June 2004

Effector mechanisms in experimental autoimmune thyroiditis (EAT) were studied in vitro by establishing a cytotoxicity system with thyroid target cells. Lymph node cells (LNC) from popliteal and inguinal lymph nodes were obtained from CBA/J mice (8-10 wk old) 12-18 d after immunization with 120 micrograms mouse thyroglobulin (MTg) in complete Freund's adjuvant (0.2 ml to both hind footpads and thighs) and were cultured with MTg (10-50 micrograms/ml). On day 5 of culture, viable LNC were added to labeled thyroid monolayers and their cytoxicity was assayed after 16 h. Functional thyroid target cells, as reflected by MTg production for up to 9 d, were prepared by adding 1 mM dibutyryl adenosine 3',5'-cyclic monophosphate and 60 microU thyroid-stimulating hormone/ml to the culture medium. On days 5-7, confluent monolayers were labeled with 111In and used as targets. Specific 111In-release ranged from 56 to 85%. The cytotoxic response is MTg specific and H-2 restricted. Pretreatment of thyroid target cells with rabbit antiserum to MTg completely inhibited cytotoxicity. Pretreatment with mouse antiserum to either Kk or Dk products resulted in approximately 50% inhibition, whereas the combined use of both antisera led to total inhibition. No cytotoxicity was observed when control BALB/c thyroid cultures were the target cells. The kinetics of the expansion of Thy-1+ cytotoxic cells by in vitro exposure to MTg were then studied. The cytotoxic response required 5 d to develop and was abolished by treating LNC on day 4 with monoclonal antibody to Lyt-1.1, but not to Lyt-2.1, plus complement. In contrast, by day 5, cytotoxicity was abrogated by similar treatment with antiserum to Lyt-2.1, but not to Lyt-1.1. We conclude that cytotoxic cells derived from MTg-immunized mice are Lyt-2-bearing cells but require the presence of Lyt-1-bearing cells for their generation and/or differentiation.
Influence of size and gene dosage on the survival of skin allografts on rats rendered tolerant at birth.
Authors: Silvers W K , Collins N H , Naji M
Published: June 2004

The attributes of the test grafts with which putatively tolerant rats are challenged influence their immune response. Lewis (Lew) rats inoculated at birth with Lew/BN F1 hybrid bone marrow cells accept large skin allografts more readily than small allografts, and F1 hybrid skin grafts survive better than BN transplants. The results indicate that the survivals of these major histocompatibility complex-incompatible grafts are determined by the same factors that operate when only weak histoincompatibilities prevail.
Identification of a B cell differentiation factor(s) spontaneously produced by proliferating T cells in murine lupus strains of the lpr/lpr genotype.
Authors: Prud'Homme G J , Park C L , Fieser T M , Kofler R , Dixon F J , Theofilopoulos A N
Published: June 2004

Lymph node and spleen cells of the autoimmune MRL/Mp-lpr/lpr mouse strain spontaneously produce (in the absence of mitogenic stimulation) a factor(s) that induces B cell differentiation. This factor is not produced by the congenic MRL/n mouse strain that lacks the lpr gene or by normal mouse strains. However, lymphoid cells of the B6-lpr/lpr (B6/1) strain also produce a B cell differentiation factor. Although the factor acts on resting B cells, its effect is greatly magnified by activating the B cells with anti-mu or lipopolysaccharide. MRL/l mice begin producing the factor as early as 1 mo of age but levels increase with age and appearance of lymphoproliferation. Cell depletion studies reveal that this factor is produced by T cells of the Lyt-1+2-phenotype. Because of its association with the lpr/lpr genotype, we term this B cell differentiation factor L-BCDF. Functional analysis of L-BCDF reveals that it acts regardless of cell density in culture and in the absence of interleukin 2 (IL-2). In fact, the increase in the production of L-BCDF by MRL/1 T cells with aging occurs concomitantly with a marked decrease in their ability to produce IL-2. No T cell replacing factor activity or B cell growth factor-like activity can be detected in MRL/l-derived supernatants. L-BCDF induces both IgM and IgG synthesis in lipopolysaccharide-activated B cells; however, it has a greater effect on IgG secretion. In particular, the production of IgG1, IgG2a, and IgG2b are markedly enhanced in the presence of L-BCDF. The spontaneous production of L-BCDF by T cells of SLE mice of lpr/lpr genotype suggests an association of this factor with autoimmunity.
Direct demonstration of the clonogenic potential of every human peripheral blood T cell. Clonal analysis of HLA-DR expression and cytolytic activity.
Authors: Moretta A , Pantaleo G , Moretta L , Cerottini J C , Mingari M C
Published: June 2004

In an attempt to determine the clonogenic properties of human peripheral blood T cells, we have developed a limiting dilution microculture system using phytohemagglutinin (PHA) as T cell activator and supernatant from PHA-stimulated spleen cultures as a source of T cell growth factors. The frequencies of cells capable of extensive proliferation under these culture conditions were 0.52-0.73, 0.98-1.11, and less than 0.02 in peripheral blood mononuclear, E-rosette-positive, and E-rosette-negative cell populations, respectively. The clonogenic potential of virtually all T cells was confirmed in experiments using single cells isolated by micromanipulation. Clone size ranged between 5 and 30 X 10(4) cells on day 14 of culture. The same microculture system was used to determine the precursor frequency of all cytolytic T lymphocytes (CTL-P). As assessed by a lectin-dependent 51Cr release assay, the CTL-P frequency in purified T cell populations ranged between 0.30 and 0.34. In comparison, the precursor frequency of T cells capable of lysing K562 target cells was ranging between 0.14 and 0.16. Parallel analysis of individual clonal cultures for both lytic activities showed that 50% of the clones exhibiting lectin-dependent lysis were also active against K562 target cells. All of the proliferating clones expressed HLA-DR antigens, although to a varying degree as assessed by flow cytofluorometry. Given the high cloning efficiency of this culture system, it appears now possible to determine the precursor frequencies of the various classes of functional cells in T cell populations.
Macrophage activation selectively enhances expression of Fc receptors for IgG2a.
Authors: Ezekowitz R A , Bampton M , Gordon S
Published: June 2004

After infection with bacillus Calmette-Guérin, peritoneal macrophages (Mø) display enhanced expression of FcR for both monomeric and complexed IgG2a, but not IgG2b. Isotype specificity of FcR can be reversed on nonactivated Mø by immune lymphokines, and IgG2a immune complexes are more effective triggers of the respiratory burst in activated Mø. Selective enhancement of IgG2a FcR by Mø activation could account for efficacy of homologous ab in mediating cytotoxicity in some systems.
Human immune interferon gene is located on chromosome 12.
Authors: Naylor S L , Sakaguchi A Y , Shows T B , Law M L , Goeddel D V , Gray P W
Published: June 2004

A cDNA clone for human immune interferon (IFN-gamma) gene sequences, plasmid p69, was used to chromosomally map the IFN-gamma gene by detecting human IFN-gamma gene sequences in DNA isolated from human-rodent somatic cell hybrids. We were able to map the IFN-gamma gene by correlating the human chromosomes present in these hybrids with the human specific 8.8 and 2.0 kilobase pair fragments produced by EcoRI digestion of genomic DNA. Southern blot analysis of 37 hybrid cell lines indicated that the gene for IFN-gamma was on human chromosome 12. A hybrid containing a portion of chromosome 12 localized the IFN-gamma gene to the p1205 leads to qter region.
Induction of acute thrombocytopenia and infection of megakaryocytes by Rauscher murine leukemia virus reflect the genetic susceptibility to leukemogenesis.
Authors: Grau G E , Puthavathana P , Izui S , Lambert P H
Published: June 2004

Acute thrombocytopenia and megakaryocyte infection have been investigated during the preleukemic phase of the disease induced by the Rauscher murine leukemia virus (RMuLV) in mice. Injection of RMuLV, either intravenously or intraperitoneally, rapidly induced thrombocytopenia, possibly as a result of direct interaction between platelets and viral particles. The susceptibility to this acute thrombocytopenia was genetically controlled and was inherited as a dominant trait. Murine strains with H-2d or H-2k haplotype, which are susceptible to the induction of leukemia by RMuLV, developed thrombocytopenia, whereas leukemia-resistant H-2b and H-2q strains of mice failed to develop thrombocytopenia. Using B10 H-2-congenic and intra-H-2-recombinant mice, it was shown that the susceptibility to RMuLV-induced thrombocytopenia was controlled by gene(s) in or closely linked to the D region of the H-2 complex. Megakaryocytes may be one of the first sites for the replication of RMuLV. Indeed, among bone marrow cells, only megakaryocytes expressed viral antigens gp70 and p30 during the initial phase of RMuLV infection. In addition, megakaryocytes from infected mice were able to transfer preleukemic thrombocytopenia as well as leukemia in syngeneic mice. The infection of megakaryocytes by RMuLV appears to be genetically controlled in a manner similar to the induction of thrombocytopenia, since only the megakaryocytes from mice developing thrombocytopenia were infected by RMuLV. These results indicate that the gene(s) governing the induction of thrombocytopenia by RMuLV may be the same gene(s) (or closely linked to the gene) that controls the susceptibility to leukemogenesis, and would be consistent with the expression of the gene product, presumably a receptor-like molecule for RMuLV, on platelet and megakaryocyte membranes.
Immune human lymphocytes produce an acid-labile α-interferon
Authors: Balkwill FR , Griffin DB , Band HA , Beverley PCL
Published: June 2004

We have described in this paper a novel human interferon (IFN) with antigenic and cross-species reactivity of α-IFN and physicochemical properties of γ-IFN. This IFN is produced by normal peripheral blood mononuclear cells during an immune response but has also been associated with autoimmune disease (10). The system described here will be useful in elucidating the biological significance and cell of origin of this IFN.
Lymphokine-activated killer cell phenomenon. II. Precursor phenotype is serologically distinct from peripheral T lymphocytes, memory cytotoxic thymus-derived lymphocytes, and natural killer cells
Authors: Grimm EA , Ramsey KM , Mazumder A , Wilson DJ , Djeu JY , Rosenberg SA
Published: June 2004

Culture of human peripheral blood lymphocytes (PBL) in partially purified and lectin-free interleukin 2 results in the generation of cytotoxic effector cells which have the unique property of lysing natural killer (NK)-resistant fresh human tumor cells. We have termed these effector cells "lymphokine- activated killer" cells (LAK). LAK are generated from both normal and cancer patients' PBL and are able to lyse both autologous and allogeneic tumor cells from all histologic tumor types tested. Our previous studies suggested that the LAK phenomenon was distinct from either the cytotoxic thymus-derived lymphocyte (CTL) or NK systems based on a variety of criteria. This study reports that the cell type involved is also distinct, as determined by phenotypic characteristics. The LAK effector cell phenotype was analyzed in parallel with alloimmune CTL, and LAK were found to be similarly susceptible to the monoclonal anti-T cell antibodies OKT-3 or OKT-8 plus complement. In contrast the LAK precursor was not susceptible to the OKT-3 or Leu-1 antibodies plus complement, while the ability to generate alloimmune CTL was totally obliterated when tested using the same PBL responder population; in fact, generation of LAK was found to be augmented five- to sixfold, clearly suggesting that LAK precursor cells are not T lymphocytes as defined by these antibodies. LAK precursors were found to be abundant in NK cell-enriched Percoll gradient fractions, which had been depleted of the 29 degrees C E- rosetting "high affinity" T cells. However, LAK precursors were found to be distinct from the majority of NK cells since lysis of fresh PBL with the monoclonal antibodies OKM-1, Leu-7, or OKT-11 significantly depleted or totally eliminated NK activity, while subsequent activation of the remaining cells generated high levels of LAK and in some cases augmented levels of LAK. LAK precursors were found to be distributed in the thymus, bone marrow, spleen, lymph node, and thoracic duct in addition to the PBL. Therefore, while the cell(s) responsible for activation and expression of LAK activity have some common features with the classic T cell-mediated CTL and NK cell systems, the LAK precursor cells are clearly distinct as determined by phenotype analysis using monoclonal antibodies and complement, and at present must be classified as a "null" cell.
Graft-vs.-host-associated immune suppression is activated by recognition of allogeneic murine I-A antigens.
Authors: Shearer G M , Levy R B
Published: June 2004

Several combinations of F1 hybrid mice were injected intravenously with parental spleen cells to determine the minimal H-2 differences between F1 and parent that are necessary to induce graft-vs.-host-associated immune suppression (GVH-associated suppression). 7-14 d after injection, the spleens of the F1 mice were tested for cytotoxic T lymphocyte potential by in vitro sensitization against trinitrophenyl-self and H-2 alloantigens. The results indicate that parental T lymphocytes must recognize I-A allogeneic determinants of the F1 recipient in order to induce suppression. Recognition of K or D alone or D with I region products other than I-A did not induce suppression. The recognition of I region without K and/or D and even the I-A difference between C57BL/6 and the B6.Cbm12 mutation resulted in immune suppression that was as potent as that resulting from the recognition of K, D, and I together. The possible significance of this function for I-A antigens is discussed with respect to three clinical examples of immune suppression for which this phenomenon may be relevant.
Synthetic Fc peptide-mediated regulation of the immune response. I. Characterization of the immunomodulating properties of a synthetic 23-amino acid peptide derived from the sequence of the CH3 domain of human IgG1.
Authors: Morgan E L , Shields J E , Campbell C S , Barton R L , Koppel G A , Weigle W O
Published: June 2004

A synthetic 23-amino acid peptide derived from the CH3 domain of human IgG1 was found to be a potent adjuvant as well as a polyclonal activator. The Fc peptide was found to enhance human and murine humoral, and T cell-mediated immune responses. Moreover, in vivo administration of Fc peptide enhanced murine natural killer cell activity. The synthetic Fc peptide was found to be more potent, on a molar basis, than native Fc fragments in inducing polyclonal antibody production and potentiating immune responses.
Suppressor T cell memory. II. The role of memory suppressor T cells in tolerance to human gamma globulin.
Authors: Loblay R H , Fazekas de St Groth B , Pritchard-Briscoe H , Basten A
Published: June 2004

The transient presence of suppressor T cell (Ts) activity in high-dose tolerance to human gamma globulin (HGG), and its (apparent) absence in low-dose tolerance, have been advanced as strong evidence against the concept that Ts play an important role in maintenance of immunological unresponsiveness. To analyze this question, CBA mice were exposed to high or low doses of deaggregated HGG (dHGG) and later challenged with HGG in immunogenic form (aHGG); their capacity to mount a primary or secondary suppressive response was assessed in an adoptive hapten-carrier system. Primary suppression reached a maximum 7 d after high-dose tolerance induction and gradually waned thereafter, being no longer detectable by day 30-35. Subsequent challenge of tolerant mice with aHGG, however, led to a rapid reactivation of suppression that bore the hallmarks of an anamnestic secondary response, and this effect was still demonstrable 135 d after tolerance induction. It was also shown that a single low dose of dHGG was capable of generating memory for suppression despite the absence of detectable primary suppression, indicating that the latter is not a prerequisite for induction of memory cells. The results were interpreted as indicating that tolerance, like immunity, is a manifestation of specific immunological memory. If tolerance to self-antigens is maintained by a similar mechanism, it would be expected that memory Ts could be induced during the early stages of fetal development. Mice were therefore exposed to tolerogen in utero by injection of their mothers with dHGG at day 7 of gestation, and were assessed at various times after birth for the capacity to exhibit primary or secondary suppression in adoptive transfer. Nonspecific suppression masked any specific effects during the first 5 wk of life. Antigen-specific, primary suppression was demonstrable subsequently until 10-12 wk of age, and if the animals were challenged with aHGG before transfer an anamnestic secondary suppressive response could be elicited up to 6 mo of age. These observations are consistent with the notion that memory Ts may play an important role in the maintenance of self-tolerance.
Inhibition of the growth of Rickettsia prowazekii in cultured fibroblasts by lymphokines.
Authors: Turco J , Winkler H H
Published: June 2004

The effect of lymphokine treatment of mouse and human fibroblast cell lines on the growth of Rickettsia prowazekii within the fibroblasts was studied. Treatment of mouse L929 cells with concanavalin A- or antigen-induced mouse lymphokines both before and after infection with R. prowazekii led to clearance of the rickettsiae from a substantial proportion of the cells and suppression of rickettsial growth in those cells which remained infected. Similar but less dramatic anti-rickettsial effects were observed in L929 cells treated with mouse lymphokines either only before or after infection with rickettsiae. Mouse lymphokine treatment of L929 cells had similar anti-rickettsial effects on the avirulent E strain and the virulent Breinl strain of R. prowazekii. Addition of cycloheximide or emetine to L929 cells at the same time as the lymphokines markedly suppressed the inhibition of rickettsial growth by the lymphokines. Mouse lymphokine treatment inhibited rickettsial survival and growth in mouse 3T3-A31 cells as well as in mouse L929 cells, but had no effect on rickettsial survival and growth in human foreskin fibroblasts. Conversely, concanavalin A-induced human lymphokines inhibited rickettsial survival and growth in human foreskin fibroblasts but had no effect on rickettsial survival and growth in mouse L929 cells. The rickettsia inhibitory activity in concanavalin A-induced mouse lymphokines was destroyed by heating the lymphokines at 80 degrees C for 10 min or by holding the lymphokines at pH 2 for 24 h but was retained after heating at 56 degrees C for 30 min.
Edema-producing activity of group A streptococcal polysaccharide and its possible role in the pathogenesis of cell wall-induced polyarthritis.
Authors: Chetty C , Brown R R , Schwab J H
Published: June 2004

Edematous responses were induced in the limbs of Sprague-Dawley rats by intravenous, intraperitoneal, or intra-articular injections of group-specific polysaccharide (PS) isolated from the cell walls of group A streptococci. After intravenous injection of the edema-producing PS, vascular permeability increase (measured by 125I-human serum albumin) was detected in the limbs, but not in the heart, lungs, spleen, liver, thymus, kidney, skin, skeletal muscle, submandibular lymph nodes, mesenteric lymph nodes, or ascending colon. This indicates a selective effect on vascular endothelium of the joints. Evidence to suggest that the edema-producing activity of the PS might play an important role in the pathogenesis of cell wall-induced polyarthritis included the following: (a) the presence of edema-producing activity in arthropathogenic cell wall preparations; (b) cell wall preparations without edema-producing activity were significantly less active in inducing arthritis than were those which contained edema-producing activity; and (c) the addition of edema-producing PS to cell wall preparations increased both the incidence and the severity of arthritis.
The major histocompatibility complex-restricted antigen receptor on T cells. I. Isolation with a monoclonal antibody.
Authors: Haskins K , Kubo R , White J , Pigeon M , Kappler J , Marrack P
Published: June 2004

An antibody-secreting B cell hybridoma, KJ1-26.1, has been prepared from mice immunized with the T cell hybridoma DO-11.10, which recognizes chicken ovalbumin in association with I-Ad (cOVA/I-Ad). KJ1-26.1 blocks I-restricted antigen recognition by DO-11.10 and a subclone of this T cell hybridoma, DO-11.10.24, which has the same specificity for cOVA/I-Ad as its parent. KJ1-26.1 does not block I-restricted antigen recognition by any other T cell hybridoma tested, including a number of T cell hybridomas closely related to DO-11.10, with similar, but not identical, specificities for antigen/I. Moreover, KJ1-26.1 binds to DO-11.10 and DO-11.10.24, but not to any other T cell hybridomas tested, including three subclones of DO-11.10 that have lost the ability to recognize cOVA/I-Ad. Thus, in every regard KJ1-26.1 appears to be binding to all or part of the receptors for antigen/I on the T cell hybridoma DO-11.10. KJ1-26.1 appears to bind to approximately 15,000 molecules/cell on the surface of DO-11.10. The antibody precipitates an 80,000 dimer from the cells, which on reduction migrates as 40-44,000 monomers. The receptor(s) for antigen/I on DO-11.10 therefore includes molecules with these properties.
Antiidiotypes against anti-H-2 monoclonal antibodies. V. In vivo antiidiotype treatment induces idiotype-specific helper T cells.
Authors: Auchincloss H , Bluestone J A , Sachs D H
Published: June 2004

Mice have been treated in vivo with xenogeneic antiidiotypes prepared against a murine monoclonal anti-H-2Kk antibody, 11-4.1. B cell immune responses have been found to be altered by such treatment as evidenced by a modification in the idiotypic repertoire of the humoral response to H-2 antigens. Transfer of purified T cells into nude mice before anti-idiotype treatment showed that T cells are involved in the induction of idiotope-bearing antibodies by xenogeneic antiidiotype. Studies using bone marrow chimeras indicate that the environment in which either T or B cells mature does not appear to alter VH region genetic control of induction of antiidiotype-induced molecules. By adoptive transfer studies, T cells from antiidiotype-treated mice were found capable of modifying the idiotypic repertoire of B cells subsequently exposed to antigen even when the T cells were obtained from antiidiotype-primed mice of inappropriate allotype. Although it still must be determined whether idiotypic or antiidiotypic T cells are involved in such B cell idiotype regulation, these results indicate that some T cell functions are altered by xenogeneic antiidiotypes prepared against B cell products and suggest that T cell immunity to major histocompatibility complex antigens may also be affected by such reagents.
Antigen-presenting cells from nonresponder strain 2 guinea pigs are fully competent to present bovine insulin B chain to responder strain 13 T cells. Evidence against a determinant selection model and in favor of a clonal deletion model of immune response gene function.
Authors: Dos Reis G A , Shevach E M
Published: June 2004

To test directly the determinant selection hypothesis of immune response gene function, we primed strain 13 T lymphocytes in vitro with allogeneic bovine insulin pulsed strain 2 macrophages. Strain 2 macrophages were found to be fully competent to present bovine insulin B chain to strain 13 T cells despite the fact that strain 2 guinea pigs are normally totally unresponsive to this antigen. These results are incompatible with a strict interpretation of the determinant selection hypothesis, which would have predicted that strain 2 macrophages would have been restricted to the presentation of A chain loop determinants. In addition, a comparison of the reactivity profiles of self-Ia- and allo-Ia-restricted strain 13 T cells to a series of synthetic B chain peptide fragments revealed that the allo-Ia-restricted populations could be activated by autologous guinea pig insulin. Taken together, these observations strongly suggest that the clonal deletion of self-reactive cells is likely to be I region restricted and that nonresponsiveness to any protein antigen may result from a restriction in the T cell repertoire that is generated during ontogeny by a clonal deletion mechanism of tolerance to self.
Ia expression by vascular endothelium is inducible by activated T cells and by human gamma interferon.
Authors: Pober J S , Gimbrone M A , Cotran R S , Reiss C S , Burakoff S J , Fiers W , Ault K A
Published: June 2004

We have used monoclonal antibody binding, measured by radioimmunoassay, fluorescence flow cytometry, and ultrastructural immunocytochemistry, to measure expression of Ia antigens on cultured human umbilical vein endothelial (HUVE) cells. Under standard culture conditions, HUVE cells do not express Ia antigens. However, treatment of primary HUVE cultures with phytohemagglutinin induces the expression of Ia antigens. Every endothelial cell in the culture becomes Ia-positive and endothelial cells appear to synthesize Ia. HLA-A,B is concomitantly increased. The expression of Ia appears to be mediated by T cells because (a) pretreatment of primary HUVE cultures with OKT3 plus complement blocks the action of the lectins but not of medium conditioned by lectin-activated peripheral blood mononuclear cells; (b) co-culture of endothelial cells with allogeneic T cells, in the absence of lectin, also induces endothelial Ia; and (c) human immune (gamma) interferon, produced by Chinese hamster ovary cells transfected with the human gamma interferon gene, directly induces endothelial Ia. During co-culture with lymphocytes, about one-third of the endothelial cells are Ia-positive after 24 h and all of the endothelial cells are Ia-positive by 72 h. Proliferation of allogeneic T cells starts by 96 h and peaks at 144 h. Thus, endothelial Ia appears sufficiently early to be a determinant for the proliferation of allogeneic T cells. Inducible expression of Ia by endothelium may be important both for allograft rejection and for recruitment of circulating T cells into the site of an immune response.
Hamster female protein. A divergent acute phase protein in male and female Syrian hamsters.
Authors: Coe J E , Ross M J
Published: June 2004

Normal adult male hamsters have low levels (10-20 micrograms) of female protein (FP) in serum which increase approximately fivefold during an acute phase response. In contrast, normal females have 50- to 100-fold higher serum levels and the acute phase reaction consists of a transient decrease in FP (approximately 50%), followed by a return to normal levels even under adverse conditions such as cortisone treatment (which by itself has a depressing effect on FP levels in normal females). The acute phase response was not inherently associated with gender, as the pattern of response could be changed to that of the opposite sex by appropriate hormonal manipulation. That is, castrated or diethylstilbestrol-treated males with high FP levels showed a female-type response whereas testosterone-treated females with low FP levels showed a male-type response. Studies on catabolism of 125I-FP showed a similar rapid half-life (T1/2, 9-16 h) in normal males and females and indicated that the sex difference in serum concentration was due to greater synthesis of FP in females. The divergent acute phase reaction of serum FP was related directly to changes in the FP synthetic rate (increased in males, decreased in females). As an indicator of serious pathology, a decrease of FP to very low levels in females was associated frequently with impending death.
Induction of tolerance in influenza virus-immune T lymphocyte clones with synthetic peptides of influenza hemagglutinin.
Authors: Lamb J R , Skidmore B J , Green N , Chiller J M , Feldmann M
Published: June 2004

Antigen-specific human T cell clones specific for defined peptides of influenza A hemagglutinin were found to be rendered unresponsive by incubation with moderately high concentrations of antigen. This was the case whether the synthetic peptide antigen was present for the duration of the culture or the cloned T cells were preincubated with antigen for 3-18 h at 37 degrees C, before stimulation with T-depleted irradiated sheep erythrocyte non-rosette-forming lymphocytes (E-) pulsed with the optimal dose of peptide. Tolerance could not be overcome by culture with various numbers of E- cells and antigen. The induction of unresponsiveness was antigen specific, since it depended upon incubation with the appropriate peptide recognized by that clone. In addition, the tolerant T cells remained unresponsive to stimulation with the specific peptide for at least 7 d after induction even though maintained in culture in the presence of T cell growth factor. This state of antigen-specific unresponsiveness is akin to immunological tolerance. Furthermore, the experiments reported here demonstrate that the helper T cell clone can be inhibited by the relevant peptide in the absence of any suppressor cells or their precursors. This suggests that antigen-induced unresponsiveness need not always depend on the presence of suppressor T cells. The induction of tolerance in T cell clones does not result in early T cell death, since cells that no longer proliferate in response to the specific antigen and accessory cells still proliferate in response to T cell growth factor.
Structural analysis of a human I-A homologue using a monoclonal antibody that recognizes an MB3-like specificity.
Authors: Giles R C , Nunez G , Hurley C K , Nunez-Roldan A , Winchester R , Stastny P , Capra J D
Published: June 2004

Monoclonal antibody IVD12 was used to isolate and characterize a human Ia molecule present on B cells that generally display DR4 or DR5 phenotypes. The specificity of binding of IVD12 to human peripheral blood B cells from 75 normal individuals and 19 homozygous human lymphoblastoid B cell lines was identical to the supertypic specificity MB3 previously defined. Furthermore, IVD12-reactivity was shown to segregate with HLA in three informative families. In each family, individuals positive for IVD12 binding were also positive for DR4 or DR5. Using IVD12, a molecule has been isolated from the homozygous cell line PRIESS (DR4/4) and has been shown by amino acid sequence analysis to be homologous to the murine I-A and human HLA-DS molecules. These findings suggest that the MB3 specificity is found on a molecule encoded by loci distinct from those loci which encode HLA-DR molecules. This molecule represents the third family of HLA-D region molecules isolated from the cell line PRIESS. Both HLA-DR and HLA-SB molecules from this cell line were previously shown by amino acid sequence analysis to be I-E-like but distinct from one another. Collectively, these data provide evidence that the HLA-D region contains at least six loci encoding distinct alpha and beta chains for the HLA-SB, HLA-DR, and HLA-DS molecules.
Role of interleukin 1 in anti-immunoglobulin-induced B cell proliferation.
Authors: Howard M , Mizel S B , Lachman L , Ansel J , Johnson B , Paul W E
Published: June 2004

In this report we describe conditions for polyclonal activation of small numbers of highly purified mouse B lymphocytes. Three signals are required for induction of DNA synthesis by the particular subset of small B lymphocytes investigated: a signal delivered by antibodies specific for the IgM receptor expressed on the B cell membrane; a signal delivered by a T cell-derived factor (B cell growth factor [BCGF]); and a signal delivered by the macrophage-derived factor interleukin 1 (IL-1). The conclusion that IL-1 has B cell co-stimulator activity is based on the findings that highly purified preparations of mouse and human IL-1 have the capacity to cause proliferation in B cells treated with anti-IgM and BCGF. Such cultures show an absolute dependence on exogenously added IL-1 when 2-mercaptoethanol is omitted from the medium. BCGF and IL-1 each act in a non-antigen-specific, non-H-2-restricted, synergistic manner. Their requirement is not observed when B cells are cultured at high density, presumably reflecting accessory cell contamination and endogenous factor production under these conditions. The B cell activation induced by these three signals is restricted to proliferation without the production of antibody-forming cells.
Relationship between expression of herpes simplex virus glycoproteins and susceptibility of target cells to human natural killer activity.
Authors: Bishop G A , Glorioso J C , Schwartz S A
Published: June 2004

Cells normally insensitive to human natural killer (NK) activity were rendered susceptible by infection with HSV-1. The cytotoxic effector cell was a nonadherent, non-T, non-B lymphocyte. Antibody plus complement treatment, using a monoclonal antibody that recognizes an antigen present on NK cells, removed much of the cytotoxic activity, and a density gradient fraction enriched for NK cells yielded cells of increased virus-specific cytotoxicity. It was concluded that the effector cell active against infected targets possessed characteristics of an NK cell. Blockage of viral protein synthesis during infection inhibited development of increased susceptibility of infected targets to NK activity. When targets were infected with a mutant virus unable to produce viral glycoprotein C (gC), NK activity against these targets was reduced approximately 30% compared with activity against targets infected with wild-type virus. Similarly, activity against targets infected in the presence of 2-deoxyglucose (2dG), which prevents cell surface expression of viral glycoprotein B (gB), was also reduced approximately 30%. An approximately 60% reduction in activity was seen against targets infected with mutant virus in the presence of 2dG; these targets express gD, but neither gB nor gC. When cells expressing various combinations of HSV-1 glycoproteins were used as both labeled targets and cold target competitors, it was found that the susceptibility of a particular target to NK activity was paralleled by its ability to act as a cold target competitor. This indicates that targets with decreased sensitivity to NK cells were less able to bind NK effectors. Further, the amount of interferon produced in co-cultures of NK effectors and infected target cells did not directly correlate with the amount of NK activity generated, and interferon pretreatment of effectors did not decrease virus-specific cytotoxicity. The present results suggest that HSV-1 glycoproteins expressed at the surface of infected targets may act as recognition structures for NK cells.
Production of auto-antiidiotypic antibody during the normal immune response. VII. Analysis of the cellular basis for the increased auto-antiidiotype antibody production by aged mice.
Authors: Goidl E A , Choy J W , Gibbons J J , Weksler M E , Thorbecke G J , Siskind G W
Published: June 2004

We have previously shown that old mice produce more hapten-augmentable plaque-forming cells (PFC) than do young animals, suggesting a greater auto-antiidiotype antibody (auto anti-Id) component in their immune response. In the present studies this is confirmed serologically. The marked auto-anti-Id response of aged mice can be transferred to lethally irradiated young recipients with spleen but not bone marrow cells from old donors, suggesting that it is an intrinsic property of their peripheral B cell population and that the distribution of Id arising from the bone marrow of old and young mice is similar. In contrast with young mice the auto-anti-Id response of old animals is relatively T cell-independent and old donors do not show an increase in their ability to transfer an auto-anti-Id response after priming with TNP-F. These observations suggest that old mice behave as if already primed for auto-anti-Id production. Irradiated mice reconstituted with bone marrow cells from either young or old donors together with splenic T cells from old donors generate a relatively large auto-anti-Id response, whereas mice reconstituted with bone marrow from either young or old donors together with splenic T cells from young donors produce few hapten-augmentable PFC. It is suggested that differences in Id expression and auto-anti-Id production are the consequences of the interaction of Id (and anti-Id) arising from the marrow with anti-Id (and Id) present in the peripheral T cell population which serves as a repository of information about shifts in Id distribution, resulting from lifelong interactions with environmental and self-antigens.
Accessory cells in murine Peyer's patch. I. Identification and enrichment of a functional dendritic cell.
Authors: Spalding D M , Koopman W J , Eldridge J H , McGhee J R , Steinman R M
Published: June 2004

Previous studies have suggested that in vitro and in vivo immune responses are defective in Peyer's patch (PP) as a result of a deficiency in accessory cell number or function. However, we report here that enzymatic dissociation of PP does release a cell population with accessory activity in oxidative mitogenesis, i.e., the proliferation of periodate-modified T cells. The accessory activity present in PP is quantitatively similar to that of spleen. Accessory function is mediated by a cell type(s) that has the following characteristics: low buoyant density, lack of adherence to plastic or glass surfaces, lack of Fc receptors, and presence of surface Ia and the 33D1 dendritic cell (DC)-specific determinants. This PP accessory cell was markedly enriched by a novel technique. PP cells formed large aggregates when cultured for 16 h with irradiated, periodate-treated spleen cells. From the clusters we obtained a low density cell population that was 60% Ia positive, 33D1 positive, non-T and non-B, Fc receptor-negative, and dendritic in morphology. The DC-enriched populations were 60-80-fold enriched in accessory function relative to unfractionated PP. We can now compare PP accessory cells with accessory cells from other organs, and try to determine how PP dendritic cells contribute to the unique functions of this lymphoid organ.
Endogenous retrovirus expression in stimulated murine lymphocytes. Identification of a new locus controlling mitogen induction of a defective virus.
Authors: Stoye J P , Moroni C
Published: June 2004

Germ line DNA from all strains of mice contains numerous endogenous retroviruses. One of these viruses, a virus with xenotropic host range is induced from lymphocytes of most strains by treatment with B cell mitogens. Virus induction is amplified by 5-bromo-2'-deoxyuridine (BrdU) treatment. We report here studies of the genetic control of retrovirus induction from lymphocytes in crosses between BALB/cTif mice and noninducible 129/Rrj mice. We identify a novel locus, Bdv-1, which controls the expression of a reverse transcriptase-positive, defective retrovirus in BALB/cTif lymphocytes. In addition, we confirm previous reports that xenotropic virus is controlled by a locus, Bxv-1, mapping to chromosome 1. The two loci are nonlinked and respond differently to inducing stimuli. Bxv-1 is induced mainly by BrdU and only marginally by mitogen; in contrast, Bdv-1 is induced by mitogen and BrdU has little effect. The induction of these two loci is discussed with respect to B cell differentiation.
Functionally restricted, allospecific, human helper T cell lines that amplify either B cell or cytolytic T cell responses.
Authors: Friedman S M , Thompson G S
Published: June 2004

Using a panel of partially cloned, OKT4+, DRw-1-specific, alloproliferative human T cell lines, we have identified two functionally restricted and reciprocating types of helper T cells. One provides major histocompatibility complex-restricted help for plaque-forming cell responses by DRw 1+ allogeneic B cells; the other preferentially amplifies the generation of allospecific cytotoxic T lymphocytes (CTL) from CTL precursors that have been suboptimally triggered by alloantigen.