bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of idiotype-specific T cell help through network perturbation.
Authors: Gleason K , Pierce S , Köhler H
Published: June 2004

Different manipulations of BALB/c mice were used to generate idiotype-specific help: neonatally induced suppression of the T 15 idiotype and low-dose priming with anti-T15 antibody. The splenic foci culture system was used to study T15-idiotype-recognizing helper T cells under limiting-cell-dose conditions. These treatments induced T15 idiotype-specific help for B cells responding to TNP-T15. Normal or hemocyanin-primed BALB/c mice did not supply T15 idiotype-specific help. The helper cells were sensitive to anti-Thy-1.2 and complement treatment and can distinguish T15 from an idiotype-different, PC-binding myeloma protein, M167, and the TNP binding myeloma protein, M460. These data show that idiotype-specific T helper cells can be induced by at least two different manipulations of the idiotype network. These manipulations presumably do not act directly on the T15-recognizing T cells, but must involve complementary idiotypic circuits that stimulate anti-T15 specific T cells. Furthermore, this study demonstrates that the splenic-fragment culture technique provides a general method to investigate, at the single cell level, idiotypic T-B cell interactions induced by perturbations of the immune network.
Role of serum IgA. Hepatobiliary transport of circulating antigen.
Authors: Russell M W , Brown T A , Mestecky J
Published: June 2004

The IgA mediated hepatobiliary excretion of antigen from the circulation was studied using a radiolabeled haptenated protein (dinitrophenyl-human serum albumin) injected intravenously in mice together with monoclonal anti-dinitrophenyl antibodies of different immunoglobulin classes. Antibodies were obtained from ascitic fluids of mice bearing the MOPC315 myeloma (IgA), or immune spleen cell hybridomas (IgG and IgM). IgA antibody brought about the transport of large amounts of antigen from the circulation to the bile during 1-3h. Analysis of bile by gel filtration showed that a large part of the transported antigen remained intact and complexed with IgA. Neither IgA of different specificity nor anti-dinitrophenyl IgM medicated biliary transport of antigen. With anti-dinitrophenyl IgG, only small amounts of low molecular weight fragments of labeled antigen were found in he bile. Preformed immune complex of radiolabeled antigen and IgA antibody were rapidly transported from the circulation to the bile, resulting in threefold-higher levels of radioactivity in bile than in serum. It is proposed that an important function of serum IgA is to mediate the hepatobiliary excretion of corresponding circulating antigens.
Induction of anterior chamber-associated immune deviation requires an intact, functional spleen.
Authors: Streilein J W , Niederkorn J Y
Published: June 2004

Anterior chamber-associated immune deviation (ACAID) expresses itself in BALB/c mice inoculated intracamerally with P815 cells in three ways: progressive growth of the tumor within the eye, transient growth of P815 cells injected subcutaneously, and prolonged acceptance of DBA/2 skin allografts. The spleen was found to play a crucial role in the development of ACAID. Splenectomized animals bearing intracameral P815 tumors reject DBA/2 skin grafts in an accelerated manner. A functioning spleen was required during the first 10 d after intracameral inoculation of P815 cells, but not thereafter. Reconstitution experiments revealed that the spleen's ability to support the induction of ACAID depends partly upon its constituent lymphoid cells, but also upon either a stromal component or a unique architectural arrangement that can only be restored with splenic fragments. The data hold promise that therapeutic protocols using appropriately timed splenectomy and specific immunization can be devised to induce hosts bearing intraocular tumors to mount an immune response sufficiently vigorous to destroy the tumor within the eye, and sufficiently precise to preserve the functional and anatomic integrity of the eye.
Contact sensitivity to azobenzenearsonate and its inhibition after interaction of sensitized cells with antigen-conjugated cells.
Authors: Thomas W R , Smith F I , Walker I D , Miller J F
Published: June 2004

Painting mice on the skin with the diazonium salt of p-arsanilic acid elicited two types of T cell activity. One was restricted by the I region of the major histocompatibility complex and was responsible for the transfer of azobenzenearsonate (ABA) sensitivity to naive mice. The other was H-2K restricted and could be demonstrated by its ability to interact specifically with ABA-coupled cells in vitro and to inhibit nonspecifically the transfer of sensitivity by cells sensitized either to ABA or to another antigen. Free antigen, or antibody directed against the cross-reactive idiotype on the anti-ABA antibodies of A/J mice, could inhibit the H-2K-restricted suppressive activity induced in the ABA immune A/J cells.
Enhancement of t lymphocyte functions by Fc fragments of immunoglobulins. I. Augmentation of allogeneic mixed lymphocyte culture reactions requires I-A- or I-B-subregion differences between effector and stimulator cell populations
Authors: Morgan EL , Thoman ML , Weigle WO
Published: June 2004

Fc fragments derived from human Ig were found to be capable of enhancing T cell-mediated, antigen-induced proliferative and mixed lymphocyte culture responses. Maximum enhancement occurred when suboptimal amounts of antigen or suboptimal numbers of stimulator cells were employed. Augmentation of the allogeneic mixed lymphocyte culture reaction requires an I-A and/or I-B subregion difference between effector and stimulator cell populations. Although a significant proliferative response was observed with K- or D- region differences, Fc fragments were unable to enhance the response. The T cell population acted upon by Fc fragments in the potentiation of these responses bears the Lyt-1(+)23(-) phenotype.
Idiotype profile of an immune response. I. Contrasts in idiotypic dominance between primary and secondary responses and between IgM and IgG plaque- forming cells
Authors: Conger JD , Lewis GK , Goodman JW
Published: June 2004

The primary response of A/J mice to p-azobenzenearsonate-keyhole limpet hemocyanin (ABA-KLH) was investigated. A day-by-day analysis at the plaque- forming cell (PFC) level was performed, with inhibition by anti-cross- reactive idiotype (CRI) serum to determine percentage of CRI(+) PFC. A regular pattern in the dynamics of Id (idiotype) dominance was observed. Just as in the NP-b and NP-a systems (9, 12), the major Id (CRI) is more dominant in primary than in secondary or hyperimmune responses. This trend is more apparent in IgG PFC which are generally 80-95 percent CRI(+) at day 10 in the primary response but only 30-40 percent CRI(+) at day 10 in secondary or hyperimmune responses. A somewhat different pattern is seen with IgM PFC. These may reach a peak of 85 percent CRI(+) in the primary response, but secondary or hyperimmune IgM PFC, which are lower in numbers than IgG PFC, remain high in CRI content at approximately 70 percent. The PFC data on extent of id dominance in secondary or hyperimmune responses is fully compatible with previously reported serological data by others. Analysis of IgG PFC by hapten inhibition indicated that heterogeneity was in the order secondary PFC {greater than} primary PFC {greater than} hybridoma AK-2.2 PFC with H(75)/H(25) values of 22.9, 6.2, and 2.7, respectively; where H(75) and H(25) are the hapten concentrations required to give 75 percent and 25 percent of inhibition of PFC, respectively. Hapten inhibition data also suggested that secondary IgG PFC were 10 times higher in median binding avidity for ABA-L-tyrosine than primary IgG PFC. The kinetic analysis strongly indicated that CRI(+) IgM PFC were preferentially switched to IgG PFC in the primary response. In both studies, the CRI content of the earliest-appearing IgG PFC was significantly higher than that of IgM PFC on that day. For example, in one case IgM PFC were 60 percent CRI + on day 6 whereas IgG PFC were 100 percent CRI(+). The high Id dominance and selective isotype switching may have either a B or a T cell basis.
Simultaneous expression of H-2-restricted and alloreactive recognition by a cloned line of influenza virus-specific cytotoxic T lymphocytes.
Authors: Braciale T J , Andrew M E , Braciale V L
Published: June 2004

Based on theoretical considerations and several types of experimental evidence with heterogeneous cell populations it has been proposed that alloreactive T cells and major histocompatibility complex (MHC)-restricted T cells directed to foreign non-NHC antigens represent overlapping subsets. In this report we provide direct evidence for this hypothesis at the clonal level. We have isolated a cloned continuous influenza virus-specific cytotoxic T cell (CTL) line derived from a single (H-2b X H-2d)F1 CTL precursor which simultaneously exhibits H-2-restricted cytotoxicity of influenza A/Japan/305/57 virus in association with H-2Kd and alloreactive cytotoxicity for H-2Kk alloantigen. Cold target inhibition data demonstrate that both MHC-restricted and alloreactive recognition is mediated by the same cell population. In addition to cross-reactivity at the target cell level, we shown that this cloned CTL line can be specifically stimulated to proliferate either by A/Japan/305/57 virus-infected cells expressing H-2Kd or by uninfected cells of the H-2Kk haplotype.
Regulation by complementary idiotypes. Ig protects the clone producing it.
Authors: Rowley D A , Griffith P , Lorbach I
Published: June 2004

A/He mice actively producing complementary or anti-idiotypic antibody directed against a combining site structure for phosphorylcholine (PC) have profound and long-lasting suppression of their response to PC. B cells from unresponsive mice are unresponsive in vitro, and attempts to demonstrate suppressor cells in unresponsive mice were unsuccessful. Although the process ultimately responsible for suppression has not been defined, suppression can be initiated by anti-idiotypic antibody alone and prevented by complementary Ig; i.e., by anti-PC antibody. Furthermore, a suppressed anti-PC response can be rescued by sublethal irradiation and anti-PC antibody given passively. The recovery of the suppressed response is slow and presumably results from maturation from "stem" cells, which are protected from tolerization by the passively given antibody. Thus, by extrapolation, one of the functions of secreted Ig may be to protect the clone that produces it.
Influence of thymic genotype on the systemic lupus erythematosus-like disease and T cell proliferation of MRL/Mp-lpr/lpr mice.
Authors: Theofilopoulos A N , Balderas R S , Shawler D L , Lee S , Dixon F J
Published: June 2004

In young adulthood, MRL/Mp-lpr/lpr mice develop severe systemic lupus erythematosus (SLE)-like syndrome associated with massive T cell proliferation. The congenic MRL/Mp- mice lack the lpr gene and develop chronic SLE late in life. We have exchanged thymic transplants between these substrains so as to determine the role of the thymus in the development of early, severe SLE and of lymphoproliferation. The median survival times of unmanipulated lpr/lpr and mice were 160 and 510 d, respectively. The lpr/lpr and mice thymectomized when newborn and transplanted at 1 mo with the opposite type of thymus retained the diseases phenotype of their unmanipulated counterparts with 50% mortality at 186 and 498 d, respectively. In contrast, lpr/lpr mice thymectomized when newborn but not transplanted with thymus did not develop lymphoid hyperplasia and glomerulonephritis, and 100% of them were alive at 390 d. Serologically, the thymectomized but untransplanted lpr/lpr mice had significantly reduced levels of autoantibodies, whereas thymectomized and transplanted mice of either substrain were similar to unmanipulated controls. The results indicate that: (a) a thymus is essential for expression of lymphoproliferation and early SLE-like disease in the lpr/lpr phenotype; (b) the lpr/lpr disease is not a result of a unique hormonal or microenvironmental defect(s) of the thymus of this substrain because the genotype of the thymus is irrelevant for the development of T cell proliferation and early SLE; (c) differentiation of stem cells under the hormonal or microenvironmental influences of a thymus that possesses the lpr genotype does not lead to abnormal T cell differentiation or early autoimmunity; and (d) the lpr/lpr disease cannot be caused exclusively by an intrinsic B cell defect or environmental stimuli that cause B cell polyclonal activation.
Antigen- and receptor-driven regulatory mechanisms. VIII. Suppression of idiotype-negative, p-azobenzenearsonate-specific T cells results from the interaction of an anti-idiotypic second-order T suppressor cell with a cross-reactive-idiotype-positive, p-azobenzenearsonate-primed T cell target.
Authors: Sy M S , Nisonoff A , Germain R N , Benacerraf B , Greene M I
Published: June 2004

The suppressor pathway that regulates the T cell response to p-azobenzenearsonate (ABA)-coupled cells has been studied. It has been found that the ability of anti-idiotypic second-order T suppressor cells (Ts2) to inhibit T cell-dependent delayed-type hypersensitivity (DTH) responses depended upon the presence of cross-reactive-idiotype (CRI)-bearing T cells present in ABA-primed mice. This suppressor T cell subset, termed Ts2, so exists with CRI-negative T cells that mediate DTH in vivo. It appears that antigen-activated CRI+ Ts3 require signals from the anti-CRI Ts2 subset to suppress DTH reactions in an idiotype-nonspecific manner. The relevance of these observations to a comprehensive scheme of T and B cell regulation is discussed.
Capacity of genetically different T lymphocytes to induce lethal graft-versus-host disease correlates with their capacity to generate suppression but not with their capacity to generate anti-F1 killer cells. A non-H-2 locus determines the inability to induce lethal graft-versus-host disease.
Authors: Van Elven E H , Rolink A G , Veen F V , Gleichmann E
Published: June 2004

When comparing, in a murine model, the kind of graft-versus-host (GVH) disease (GVHD) induced by the donor strain DBA/2 on the one hand and several H-2-congenic resistant B10 donor strains on the other, we found that strain DBA/2 was a universal nonkilling GVH donor for H-2-incompatible nonirradiated F1 hybrid recipients. In this respect, DBA/2 T cells differed from those of the H-2-identical donor strain B10.D2 as well as those of other b10 donor strains. The inability of strain DBA/2 to kill by GVH reaction was not limited to certain H-2 incompatibilities in the F1 recipients, but was nonspecific. The inability to kill is determined by a dominant locus not linked to H-2. DBA/2 T cells were also incapable of inducing the severe suppression of hematocrit values, bone marrow erythropoiesis, thymic cell proliferation, and splenic IgG production in the F1 recipients that was observed after the injection of T cell from the B10 strains. However, DBA/2 T cells, in contrast with those of the B10 donor strains, were vigorous stimulators of IgG production in H-2-incompatible F1 hybrid recipients. Surprisingly, strain DBA/2 as well as the B10 donor strains had good capacity to generate anti-F1 TK cells. Taken together, these findings raise the possibility that lethal GVHD disease is not caused, or not caused exclusively, by donor killer T cells, but by those donor T cells that directly or indirectly induce a suppression of cell proliferation in certain vital organs of the recipient.
H-2 restriction as a consequence of intentional priming. Frequency analysis of alloantigen-restricted, trinitrophenyl-specific cytotoxic T lymphocyte precursors within thymocytes of normal mice.
Authors: Stockinger H , Bartlett R , Pfizenmaier K , Röllinghoff M , Wagner H
Published: June 2004

An in vitro acute-depletion protocol was used to detect trinitrophenyl (TNP)-specific, allo-major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) within thymocytes of inbred mice. After removal of alloreactivity, the negatively selected cells could be sensitized to become TNP-specific, allo-MHC-restricted cytotoxic T cells. A precursors frequency analysis revealed a three- to ninefold lower frequency of allo-MHC-restricted CTL precursors (CTL-P) as compared to self-MHC-restricted CTL-P. The specificity analysis of clonally distributed allo-MHC-restricted CTL-P excluded cross-reactivity as an explanation of allo-MHC restriction. These results provide direct evidence that thymic T cells are composed of a mixture of self-MHC- and allo-MHC-restricted immunocompetent T cells and that antigen-driven selection of precommitted T cells dictates the H-2-restriction phenotype, i.e., H-2 restriction is a consequence of priming.
Characterization of a spontaneous disease of white leghorn chickens resembling progressive systemic sclerosis (scleroderma).
Authors: Gershwin M E , Abplanalp H , Castles J J , Ikeda R M , van der Water J , Eklund J , Haynes D
Published: June 2004

University of California, Davis (UCD) line 200 White Leghorn Chickens spontaneously develop a syndrome that has many analogous features to human progressive systemic sclerosis. This syndrome is characterized by progressive involution of comb, dermal fibrosis, and distal polyarthritis. These three features occur within 6 wk after hatching, and are accompanied by a 40% mortality as a result of vaso-occlusive disease, with development of secondary infection of peripheral gangrenous lesions. Birds that survive greater than 2 mo after hatching progressively develop fibrosis of the esophagous and mononuclear infiltration of heart and kidney, with prominent occlusion of small and medium sized blood vessels. In addition, line 200 chickens develop rheumatoid factors, antinuclear antibodies, and antibodies to collagen, but do not have antibodies to thymocytes, DNA, or extractable nuclear antigens. Moreover, antinuclear antibodies when studied using HEp-2 cells as substrate demonstrate predominantly a speckled pattern. This syndrome of line 200 chickens is not detectable in F1 crosses to several UCD inbred lines. F1 X parental line BC1 backcrosses have an approximately 50% incidence of disease, suggesting that this syndrome is inherited as autosomal recessive. However, only 4% of F2 generation birds show abnormal symptoms, suggesting the presence of modifying genes. There is no appearance of IgG deposition, as determined by immunofluorescence, in either skin, blood vessels, esophagus, or heart. However, approximately 20% of chickens have a glomerulonephritis; this feature appears to be a terminal event and does not appear clinically significant. Although this syndrome of line 200 chickens has several features that are in sharp distinction to human scleroderma, the presence of common immunologic and pathologic denominators suggest that this spontaneous disease may be an appropriate model to develop a better understanding of autoimmune connective tissue diseases.
Induced tolerance in F1 rats to anti-major histocompatibility complex receptors on parental T cells. Implications for self tolerance.
Authors: Bellgrau D , Smilek D , Wilson D B
Published: June 2004

The immunogenicity of cell surface markers associated with specific anti-major histocompatibility complex (MHC) alloreactivity of rat peripheral T lymphocyte subpopulations has been demonstrated in the past by the ability of such cell populations to induce a profound and specific resistance to systemic graft-vs.-host (GVH) disease in adult rats. Our studies demonstrate that these specificity-associated anti-MHC parental strain T cell markers are also tolerogenic; if small numbers of parental strain T cells are administered to newborn F1 rats, they result in the specific inability to induce GVH resistance later on in adult life. Moreover, unlike normal animals, these F1 rats are extremely sensitive to systemic GVH disease caused by T cells from the original donor parental strain.
Mechanism of action of the C4 nephritic factor. Deregulation of the classical pathway of C3 convertase.
Authors: Gigli I , Sorvillo J , Mecarelli-Halbwachs L , Leibowitch J
Published: June 2004

Three mechanisms that regulate the formation and function of the classical pathway C3 convertase (C4b2a) have been elucidated: (a) an intrinsic decay of the enzyme that is temperature dependent; (b) an extrinsic decay mediated by the effect of the serum protein C4b binding protein (C4-bp); and (c) inactivation of C4b by the proteolytic action of C4b/C3b inactivator (C4b/C3bINA), which cleaves that alpha' chain of C4b to yield C4d (alpha 2) and C4c (alpha 3, alpha 4, beta, and gamma chains). A fourth mechanism described here is based on the observation that the IgG fraction of the serum of certain patients with glomerulonephritis contains a protein termed C4 nephritic factor (NFc), which prevents the intrinsic decay of C4b2a. This protein, which prolongs the half-life of surface-bound C4b2a from 7.5 min to greater than 5 h, increases the use of C3 and C5. It also inhibits the decay produced by C4-bp by preventing the dissociation of C2a from the C4b2a complex. Additionally, the C2b/C3bINA alone, or in the presence of C4-bp, fails to cleave the alpha' chain of C4b in the surface-bound stabilized C4b2a complex. This protective property of NFc requires the presence of C2a, because C4b was not protected unless it was bound to C2a. Thus in the presence of NFc, the three natural controls of the function of the classical pathway convertase, intrinsic decay, extrinsic decay, and proteolytic cleavage, are bypassed.
Studies of the cell surface of mouse dendritic cells and other leukocytes
Authors: Nussenzweig MC , Steinman RM , Unkeless JC , Witmer MD , Gutchinov B , Cohn ZA
Published: June 2004

The surface of dendritic cells (DC) has been analyzed by means of monoclonal antibodies (Ab) and lactoperoxidase (LPO)-mediated radioiodination. Antigens and other exteriorily disposed polypeptides of purified spleen DC were compared with those of tissue macrophages (Mφ), monocytes, and other bone marrow-derived elements.

Quantitative binding studies and autoradiography with (125)I-Ab established that DC expressed high levels of I-A and H-2D, 2 × 10(5) and 1 × 10(5) Ab binding sites per cell, respectively. DC from conventional, germ-free, and specific pathogen-free mice were all rich in Ia. Expression of Ia on B cells was 5-10 percent of that on DC and increased fivefold during lipopolysaccharide mitogenesis. More than 70-90 percent of purified Mφ and monocytes from specific pathogen-free mice were Ia negative, but increased levels of Ia were noted on cells from mice reared under conventional conditions. Thus large amounts of Ia on DC is a constitutive trait, whereas the expression of Ia by other cell types may be governed by the environmental and immunological status of the host.

The 2.4G2 Fc receptor Ag was not detected on DC. Peritoneal and spleen Mφ had 10(5) 2.4G2 binding sites/cell, whereas monocytes and lymphocytes were less reactive (1 × 10(4)-3 × 10(4) binding sites/cell).

Four other Mφ-related antigens were evaluated. Each had a distinctive tissue distribution and none bound exclusively to Mφ and monocytes. Neither 1.21J (Mac-1) nor F4/80 reacted with DC. Immunoprecipitation studies of externally ((125)I) and biosynthetically ([(35)S]methionine)dabeled cells confirmed the binding data.

Sensitive binding assays with (125)I-Ab confirmed previous observations that DC lack Ig and Thy-1. Lyt-1 was also not found on DC, but 5-12 percent of the cells in purified DC preparations expressed both Lyt-2 and Ia. All DC expressed the leukocyte common antigens at levels similar to other leukocytes.

The spectrum of surface polypeptides labeled by LPO-mediated iodination was different on Mφ, DC, and lymphocytes. Polypeptides migrating at molecular weights of 155,000, 85,000, and 62,000 appeared to be restricted to DC.

These observations establish that the cell surface of DC differs considerably from other leukocytes, including the blood monocyte, and suggest that the DC is part of a unique Ia-rich leukocyte differentiation pathway.
Antibodies to membrane structures that distinguish suppressor/cytotoxic and helper T lymphocyte subpopulations block the mixed leukocyte reaction in man.
Authors: Engleman E G , Benike C J , Glickman E , Evans R L
Published: June 2004

Two major subsets of human T lymphocytes that are functionally analogous to the mouse Lyt-2+ and Lyt-2- subsets have been defined by their expression of two thymus-dependent membrane antigens, Leu-2 and Leu-3. Leu-2+,3- cells have suppressor/cytotoxic functions and Leu-2-,3+ cells have helper functions. These studies were designed to determine the effects of adding IgG1 monoclonal anti-Leu-2 and anti-Leu-3 antibodies to the mixed leukocyte reaction (MLR). At high concentrations, each antibody partially inhibited the proliferative response of unseparated T cells and abolished the response of the isolated subset having the appropriate phenotype. An IgG1 monoclonal antibody to HLA-A2 and an IgG2a antibody to Leu-1, a pan-T antigen, failed to inhibited the MLR. These results suggest that the Leu-2 and Leu-3 antigens may have a direct role in the mechanism whereby T cells recognize and respond to alloantigen.
Enhancement of delayed hypersensitivity reaction with varieties of anti-cancer drugs. A common biological phenomenon.
Authors: Goto M , Mitsuoka A , Sugiyama M , Kitano M
Published: June 2004

Delayed hypersensitivity reaction in mice was commonly enhanced with various anti-cancer agents administered as single or intermittent high doses but not consecutive divided doses. The effect of anti-cancer agents on the delayed hypersensitivity reaction was thought to be due to elimination of suppressor T cell activity.
Haplotype-specific suppression of antibody responses in vitro. II. Suppressor factor produced by T cells and T cell hybridomas from mice treated as neonates with semiallogeneic spleen cells.
Authors: Sorensen C M , Pierce C W
Published: June 2004

Culture supernatant fluids from spleen cells from C57BL/10 or BALB/c mice neonatally treated with semiallogeneic (B 10.D2 x B10)F1 cells to induce haplotype-specific suppressor T cells and restimulated with macrophages syngeneic at I-A with the allogeneic haplotype encountered as neonates contain a soluble factor capable of suppressing primary in vitro antibody responses of normal syngeneic spleen cells in a non-antigen-specific manner. This haplotype-specific suppressor factor, TsF-H, has also been recovered in culture fluids of a T cell hybridoma produced by fusion of the AKR thymoma BW5147 and the haplotype-specific suppressor T cells. TsF-H is inactivated by low pH (3.5) trypsin, for 30 min at 50 degrees C, and has a molecular weight in the range of 45,000 to 68,000. Studies with specific immunoabsorbents demonstrate the presence of determinants encoded by the I-A subregion of the haplotype of the T cell producing TsF-H but not I-J subregion or immunoglobulin constant-region determinants on the TsF-H. Suppression is restricted to primary in vitro antibody responses, and not secondary antibody, mixed lymphocyte, or cytotoxic lymphocyte responses by spleen cells syngeneic at the I-A subregion of H-2 with the T cell producing the factor. The properties and activities of TsF-H and the haplotype-specific suppressor T cell are compared and contrasted with antigen-specific and genetically restricted suppressor T cells and their factors.
Binding of bacillus Calmette-Guérin-activated macrophages to tumor targets. Selective inhibition by membrane preparations from homologous and heterologous neoplastic cells.
Authors: Marino P A , Whisnant C C , Adams D O
Published: June 2004

The binding of tumor cells by activated macrophages is an initial and necessary event in the cytolysis of these targets. The data here indicate that membrane preparations from RL sigma 1 leukemia targets, EL-4 lymphoma targets, and P815 mastocytoma targets each inhibited binding of its homologous target to bacillus Calmette-Guérin (BCG)-activated murine macrophages in a dose-dependent fashion. Similar amounts of membrane from lymphocytes did not alter binding of the three neoplastic target to BCG-macrophages. Membranes of the three targets also inhibited binding of the heterologous neoplastic targets. Inhibitory activity of membrane preparations from P815, EL-4, and RL sigma 1 targets could be adsorbed by incubation of limiting concentrations of the membrane preparations with BCG-activated macrophages but not with thioglycollate broth-elicited macrophages. Exposure of BCG macrophages to membrane preparations from RL sigma 1, FL-4, or P815 targets inhibited subsequent cytolysis of the three targets. Inhibitory activity was increased in preparations enriched for plasma membrane. The data suggest that binding of three murine, nonadherent neoplastic targets to BCG-activated murine macrophages is mediated, in part, by recognition structures present within the plasma membranes of the three targets.
Human megakaryocytes. II. Expression of platelet proteins in early marrow megakaryocytes.
Authors: Rabellino E M , Levene R B , Leung L L , Nachman R L
Published: June 2004

Analysis of various platelet proteins by immunofluorescence demonstrated that platelet glycoproteins Ib, IIb, and IIIa, as well as plasma factor VIII antigen (factor VIII:AGN), platelet factor 4, and fibronectin are present in the vast majority of morphologically recognizable megakaryocytes. In addition, a small number of lymphoid-like mononuclear marrow cells, representing approximately 1.4--2.9/10(4) marrow cells, was found to express the same platelet proteins. This population of early marrow megakaryocytes is analogous to small acetylcholinesterase-positive rat and mouse marrow cells. Fc receptors for IgG were expressed in all megakaryocytes and megakaryocyte precursors, whereas the Ia antigen was detected only on a proportion of mature megakaryocytes and not on only early or precursor megakaryocytes. Platelet glycoproteins Ib, IIb, and IIIa, as well as factor VIII:AGN, and platelet factor 4 were established as distinct markers for marrow megakaryocytes and may be helpful for identifying megakaryocytic cells as well as for monitoring events of megakaryocyte differentiation.
Treatment by limited surgery and specific immunization of guinea pigs with stage II experimental cancer.
Authors: Hunter J T , Ashley M P , Sukumar S , Sugimoto T , Zbar B , Rapp H J , Yarkoni E
Published: June 2004

The malignant disease produced in guinea pigs by intradermal inoculation of line-10 was allowed to progress to stage II, at which time the dermal tumor and the first draining lymph node were grossly evident. At that stage, the external appearance of the next draining lymph node was normal, but it contained tumor cells. Limited surgery consisting of excision of the dermal tumor and first draining lymph node was not curative; palpable metastases developed in the second and other draining lymph nodes, and at autopsy, some animals were found to have gross, visible lung metastases. Immunization of guinea pigs with a mixture of irradiated syngeneic tumor cells plus mycobacterial cell walls in an oil-in-water emulsion eradicated tumor cells remaining in lymph nodes after limited surgery for stage II experimental cancer and prevented progression of the disease to stage III. Tumor intravenously implanted in the lungs of animals after limited surgery for stage II disease was also eliminated by immunization.
Loss of tumor-specific and idiotype-specific immunity with age.
Authors: Flood P M , Urban J L , Kripke M L , Schreiber H
Published: June 2004

The ultraviolet light-induced fibrosarcoma 1591 undergoes "first-set rejection" when transplanted into normal syngeneic mice. We found, however, that the primary resistance of normal mice decreases with age, beginning at 9--12 mo, equivalent to middle age for mice. Mice lose with age the capacity to mount both idiotypic and anti-idiotypic responses responsible for controlling the growth of tumor. This loss was correlated with quantitative as well as qualitative changes in the response, such as changes in specificity and clonotype. Normal young mice regularly expressed a dominant common anti-1591 "idiotype" as defined by an anti-idiotypic probe. The capability of normal mice to respond with lymphocytes of this dominant common idiotype began to decline at about 8 mo of age. At this time, animals still generated tumor-specific lymphocytes, but these lymphocytes appear to be idiotypically different lymphocyte clones. With further increase in age, animals responded with tumor-reactive lymphocytes that showed a marked cross-reactivity to other tumor target cell lines. Both in vivo and in vitro, the capability of normal mice to mount an immune response that was specific for the 1591 tumor cells decreased between 9 and 14 mo, which was the age individual mice became increasingly susceptible to a challenge with 1591 tumor cells. Thus, our data suggest that clones of tumor-specific T cells provide primary and early protection of young animals against challenge with malignant 1591 cells. However, the dominance of these tumor-specific T cell clones in a primary immune response is lost in middle-age. Because the ability of animals to mount anti-idiotypic immune response also declined in middle-aged animals, it is possible that the observed loss of clonal dominance of tumor-specific clones with increasing age is at least partially related to age-dependent changes in the anti-idiotypic compartment.
Augmentation of macrophage complement receptor function in vitro. III. C3b receptors that promote phagocytosis migrate within the plane of the macrophage plasma membrane.
Authors: Griffin F M , Mullinax P J
Published: June 2004

We have previously reported that treatment with a unique lymphokine enables resident mouse peritoneal macrophages to phagocytize via their complement receptors and we have presented evidence that the lymphokine act by enabling complement receptor engagement by C3b ligands to generate a phagocytic signal, thereby linking the cell surface binding event with the intracellular phagocytic machinery. In the present experiments, we used immobilized immune complexes to study the topography of C3b receptors of resident mouse peritoneal macrophages treated with the lymphokine. Our results indicate that lymphokine treatment enables the macrophages' C3b receptors to migrate within the plane of the cells' plasma membrane and that manipulations of macrophages that abrogate one response to the lymphokine, complement receptor mobility, also abrogate the other response, complement receptor-mediated phagocytosis. These findings strongly suggest that lateral mobility of a ligand-bound receptor within the macrophage plasma membrane is an essential component of the phagocytic signal. Moreover, our results indicate that the difference in complement receptor function among various populations of macrophages is not due to the expression of different types of complement receptors by the different macrophage populations but rather to a difference in the relationship of the C3b receptor with other plasma membrane or intracellular components.
Quantitation and clonal isolation of cytolytic T lymphocyte precursors selectively infiltrating murine sarcoma virus-induced tumors.
Authors: Brunner K T , MacDonald H R , Cerottini J C
Published: June 2004

A limiting dilution mixed leukocyte-tumor cell microculture system was used to quantitate cytolytic T lymphocytes and their precursors (CTL-P), which infiltrate tumors induced by injection of Moloney sarcoma-leukemia virus (MSV-MoLV) complex into C57BL/6 mice. Leukocyte populations obtained from tumors collected on day 10 after virus injection were found to contain significantly higher frequencies of operationally defined (tumor-specific) CTL-P than either peripheral blood leukocytes (PBL) or spleen cells from the same animals. When these frequencies were normalized according to the content of Lyt-2+ T cells in each tissue, average CTL-P frequencies were found to be 1/9 in tumor-infiltrating cells vs. 1/41 in PBL. These results directly demonstrate selective accumulation of CTL-P in the tumor mass. A number of clonal isolates obtained from tumor-infiltrating leukocyte populations were expanded and studied for cytolytic activity and specificity. Of 11 isolates, 10 were found to have high cytolytic activity, leading to 50% lysis of the syngeneic MoLV-derived tumor target cells in 3.5 h at lymphocyte:target cell ratios ranging from 0.5:1 to 3.2:1. Furthermore, five randomly selected clones showed H-2 restriction by their selective lytic activity against MoLV-derived syngeneic MBL-2 target cells and their lack of activity against either MoLV-derived allogeneic (LSTRA) tumor cells or against syngeneic (EL4) or allogeneic (P815) target cells unrelated to MoLV.
Induction of plasminogen activator synthesis by antibodies.
Authors: Becker D , Ossowski L , Reich E
Published: June 2004

We have purified the immunoglobulins (IgG) from rabbit antisera raised against two cell lines--LLC-PK1 derived from pig kidney and from Kirsten sarcoma virus-transformed BALB/3T3--and have studied the effects of IgG on cultures of the respective target cells. The following observations were made with both cell types: (a) The addition of purified IgG produced a rapid change in morphology within 2 h. This consisted of cell rounding, agglutination, and detachment from the surface of the dish. (b) Beginning approximately 2 h after IgG addition there was a progressive rise in plasminogen activator production for 24--36 h. (c) Both the morphological change and the induction of plasminogen activator (PA) synthesis were reversible and required the continued presence of IgG for their maintenance. The increase in PA production, but not morphological change, depended on genetic transcription and translation, being inhibited by actinomycin and/or cycloheximide. (d). These effects of IgG were specific: they were not observed with preimmune or indifferent IgG and occurred only after interaction between an IgG preparation from antisera and the cells used to generate the particular antiserum. The divalent IgG fragments F(ab')2 retained fully the activities of the native IgG molecules from which they were derived.
Immunochemical studies of conjugates of isomaltosyl oligosaccharides to lipid. I. Antigenicity of the glycolipids and the production of specific antibodies in rabbits.
Authors: Wood C , Kabat E A
Published: June 2004

Isomaltose oligosaccharides varying in size from two sugars, isomaltose (IM2), to seven sugars, isomaltohepatose (IM7), were coupled to stearylamine by reductive amination with sodium cyanoborohydride. Each compound was purified by column chromatography to yield a series of glycolipids containing oligosaccharides differing in length. Stearyl-isomaltotriose to stearyl-IM7 could be incorporated into liposomes and could render them agglutinable by specific antibodies to alpha 1 leads to 6 dextran and could be lysed if complement was also added, whereas those containing stearyl-IM2 were not agglutinated or lysed, indicating that stearyl-IM2 may not be protruding from the liposome surface sufficiently to react with the antibody. Stearyl-isomaltosyl oligosaccharides by themselves or incorporated into liposomes were equally antigenic when emulsified in complete Freund's adjuvant. They elicited pauciclonal responses, and the antibodies were alpha 1 leads to 6 specific, cross-reacted with dextran, and gave semirestricted isoelectric focusing patterns.
Lymphokine-mediated bone resorption requires endogenous prostaglandin synthesis.
Authors: Bockman R S , Repo M A
Published: June 2004

Enhanced synthesis of prostaglandin (PG) E by explanted fetal rat bones was initiated by lymphocyte-conditioned media but not by physiological levels of parathyroid hormone. Rapid release of PGE from bone occurred only when the lymphokine was present. Synthesis of PGE preceded and was necessary for the bone resorption caused by the lymphokine preparation. Local production of prostaglandins in response to inflammatory cell or tumor-derived factors may in part be responsible for the localized bone loss that occurs in certain pathological states.
Auricular chondritis in rats. An experimental model of relapsing polychondritis induced with type II collagen.
Authors: Cremer M A , Pitcock J A , Stuart J M , Kang A H , Townes A S
Published: June 2004

Outbred Wistar rats immunized with native type II collagen developed ear lesions resembling those of human relapsing chondritis. As in human disease, these lesions were characterized by intense chondritis, positive immunofluorescence reactions to IgG and C3, and circulating IgG reactive with native type II collagen. Furthermore, electron-dense deposits were seen near the surface of chondrocytes and corresponded with deposits of IgG and C3. These observations suggest a causal relation between humoral immunity to type II collagen and auricular chondritis in the rat and support the hypothesis than human relapsing polychondritis is an autoimmune disease mediated by immunity to type II collagen.
Cytolytic T lymphocyte function is independent of growth phase and position in the mitotic cycle
Authors: Sekaly RP , MacDonald HR , Zaech P , Glasebrook AL , Cerottini J-C
Published: June 2004

We have investigated mitotic cell cycle and growth phase regulation of homogeneous cytolytic T lymphocytes (CTL). Two independently derived CTL clones were stained with the DNA-binding dye Hoechst 33342, sorted in a fluorescence-activated cell sorter according to their position in the cell cycle, and then assayed for specific lytic activity using a short-term (30 min) (51)Cr release assay. Results show that lytic activity remained unchanged throughout the cell cycle. Furthermore, there was no significant difference in the lytic activity of CTL clones growing exponentially or arrested in a plateau phase. These results demonstrate that T cell-mediated cytolysis is independent of growth phase and position in the cell cycle.
Studies of endotoxin-induced decrease in lipoprotein lipase activity.
Authors: Kawakami M , Cerami A
Published: June 2004

A variety of invasive stimuli have been shown to induce hyperlipidemia due to impaired removal of triglyceride from the circulation. The mechanism by which endotoxin induces a deficiency in the activity of the key enzyme of triglyceride metabolism, lipoprotein lipase (LPL), has been studied. In C3H/HeN (endotoxin-sensitive) mice, LPL activity in adipose tissue was markedly suppressed 16 h after endotoxin administration. In contrast, the endotoxin-resistant C3H/HeJ mice were less sensitive to the suppressive effect of endotoxin on LPL activity. After endotoxin administration, a transferable factor had been detected in the blood of C3H/HeN mice 2 h after the injection of endotoxin that causes a suppression of adipose tissue LPL activity in C3H/HeJ mice as well as in C3H/HeN mice. Conditioned medium from the cultures of peritoneal exudate cells of C3H/HeN mice incubated in endotoxin also suppresses adipose tissue LPL in C3H/HeJ mice. These studies demonstrate that exudate cells produce a humoral factor in response to endotoxin, which suppresses adipose tissue LPL.
Antigen recognition. V. Requirement for histocompatibility between antigen-presenting cell and B cell in the response to a thymus-dependent antigen, and lack of allogeneic restriction between T and B cells.
Authors: Nisbet-Brown E , Singh B , Diener E
Published: June 2004

The restrictions imposed by the major histocompatibility complex on T-B-antigen-presenting cell (APC) interactions were studied with an in vivo adoptive transfer system, using mutually tolerant T and B cells taken from one-way fetal liver chimeras. It was found that the B cells and adoptive recipient (which provides APC function) have to share determinants encoded by the left-hand end of the H-2 complex for cooperation, whereas there is apparently no such requirement for T-B cell syngeneicity. Suppression arising from allogeneic effects between the host and the transferred T or B cells was excluded by the use of tolerant as well as normal adoptive recipients; both were functionally equivalent. We conclude that under experimental conditions, unrestricted helper T cell function and concurrent APC-B cell genetic restriction can be demonstrated in vivo.
Expression of the macrophage-specific antigen F4/80 during differentiation of mouse bone marrow cells in culture.
Authors: Hirsch S , Austyn J M , Gordon S
Published: June 2004

We have defined the expression of the macrophages (m phi)-specific antigen (Ag) F4/80 during differentiation in culture. The progenitor cells-the colony-forming unit in culture and cluster-forming cell-lacked Ag F4/80 but gave rise to colonies of F4/80-positive adherent m phi, as shown by fluorescence-activated cell sorting and clonal assays with L cell-conditioned medium as the source of growth factor. Ag F4/80 first appeared on a nonadherent precursor found in mass liquid BM cultures after 3 d. Once adherent, m phi expressed high levels of Ag F4/80 and other markers. The role of L cell-conditioned medium and of adherence on expression of Ag F4/80 was also examined. Clonal analysis of F4/80 and other Ag, Mac-1, and 2.4G2 (FcR) showed that all cells in all independent colonies come to express these markers. These studies establish that F4/80 is a marker for the more mature stages of m phi development and that Ag expression increases progressively during maturation in vitro. Heterogeneity of Ag expression can be ascribed to variation in development and not to independent subsets of the m phi.
Mechanisms of idiotype suppression. IV. Functional neutralization in mixtures of idiotype-specific suppressor and hapten-specific suppressor T cells.
Authors: Kim B S , Greenberg J A
Published: June 2004

Specific tolerance to phosphorylcholine (PC) can be induced in BALB/c mice by neonatal injection with either pneumococcal C-polysaccharide (PnC) or anti-TEPC 15 idiotype (T15Id) antibody specific for the major idiotype (Id) of anti-PC antibody. Spleen cells from these tolerant mice exhibited T cell-mediated active suppression of anti-PC response when they were co-cultured with normal spleen cells. Suppressor cells from the PnC-injected mice appeared to bear either Lyt-1 or Lyt-2 antigens, whereas suppressor cells from anti-Id-treated mice expressed Lyt-2 antigens. Analyses of the specific receptors of these suppressor T cells, based on either adherence to PC and T15-coated petri dishes or cytolysis by rabbit anti-T15Id and monoclonal IgM anti-PC antibody with complement, revealed that receptors of PnC-induced suppressor T cells recognize PC, whereas receptors of anti-Id-induced suppressor T cells react with the T15Id. The possible interaction of the two different types of suppressor T cells was examined by co-culturing normal spleen cells with mixtures of the different suppressor cell types in various cell ratios in the presence of the T-independent PC-antigen, R36a. A brief incubation of anti-Id-induced, T15Id-specific suppressor T cells with PnC-induced, hapten-specific, and T15Id-bearing suppressor T cells resulted in complete cancellation of their suppressor function. These results suggest that idiotype network regulation may also occur among suppressor T cell population.