bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of cyclosporin A on T cell immunity I. Dose‐dependent suppression of different murine T helper cell pathways
Authors: Fukuzawa Masahiro , Shearer Gene M. 
Published: March 2007

AbstractCyclosporin A (CsA) is used as a clinical immunosuppressive agent. Despite its immunosuppressive potential, some studies involving in vivo administration of cyclosporin have failed to verify the immunosuppressive activity of this agent. The present study investigates the effect of different concentrations of CsA added in vitro, or of different doses of CsA administered in vivo, on the ability of murine spleen cells to produce interleukin 2 and to generate cytotoxic T lymphocytes in vitro when stimulated with TNP‐self or H‐2 alloantigens. The results indicate that self Ia‐restricted T helper (Th) cells are more sensitive to lower doses of CsA than Th cells that are allorestricted. Thus, doses of CsA were found (15–30 mg/kg) that inactivated self Ia‐restricted Th function, but not other Th or effector function. This Th cell defect could be partially corrected in vitro by addition of Th cell factors to the sensitization cultures. A higher dose (75 mg/kg) of CsA inactivated all detectable T cell responses, and this defect was not corrected by addition of Th cell factors. T cell function returned to normal levels within two weeks of cessation of CsA at all three doses of CsA tested. The selective loss of L3T4 Th function at the lower doses of CsA was associated with a radiosensitive, Ly‐2 suppressor T cell that was selective in its action on self Ia‐restricted Th cell function. Loss of all T cell function at the higher dose of CsA was associated with a radioresistant non‐T suppressor cell that inactivated all T cell function tested. These results are discussed with respect to the selective dose‐dependent effects of CsA on Th subsets, on the activation of suppressor cells with similar selectivity, and the implications of these findings on the use of CsA to prevent rejection of tissue allografts.
SC5b‐7, SC5b‐8 and SC5b‐9 complexes of complement: ultrastructure and localization of the S‐protein (vitronectin) within the macromolecules
Authors: Preissner Klaus P. , Podack Eckhard R. , Müller‐Eberhard Hans J. 
Published: March 2007

AbstractPurified terminal components of the complement system were used together with purified S‐protein, the inhibitor of the membrane attack complex, to generate the soluble complexes SC5b‐7, SC5b‐8 and SC5b‐9. These complexes were purified by ultracentrifugation in sucrose density gradients with 50–70% yield, exhibiting sedimentation coefficients of 20 S, 21 S and 23 S, respectively. In Ouchterlony double‐diffusion analysis, the purified complexes gave a line of identity against all antisera of the precursor components indicating that complex formation had occurred. The identity of the complexes was also revealed by the appearance of all subunit components after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Since the inhibitor function of S‐protein in the terminal complement cascade should also be manifested in the morphology of the macromolecules generated, the ultrastructures of the three complexes were analyzed by electron microscopy. In contrast to aggregated (C5b‐7)n and (C5b‐8)n, negatively stained SC5b‐7 and SC5b‐8 imaged mostly as monomeric irregularly shaped cylindrical structures, whereas SC5b‐9 < 27 S) appeared as wedge‐shaped structure lacking the tubular polymerized C9. (All three complexes were also generated in the presence of biotinyl‐S‐protein and labeled with avidin‐gold conjugates as electron‐dense marker). Analysis of the modified complexes in electron micrographs demonstrated that the complexes were marked exclusively at one site of their ultrastructures, suggesting this region to be the location of S‐protein and the critical site for membrane binding of C5b‐7 or C5b‐8 and for initiation of C9 polymerization. These results support recent findings in which the function of S‐protein as complement inhibitor was dependent on conformational changes of the protein molecule with concomitant exposure of the heparin‐binding domain.
Peripheral tolerance mechanisms prevent the development of autoreactive T cells in chimeras grafted with two minor incompatible thymuses
Authors: Zamoyska Rose , Waldmann Herman , Matzinger Polly 
Published: March 2007

AbstractThe thymus has been shown to play an important role in the generation of T cell tolerance to self antigens. Developing T cells are readily tolerized to antigens which are expressed in the thymus, and it is generally thought that such thymic tolerance occurs by a mechanism of clonal deletion. We sought to examine whether T cells which initially encountered a “self antigen” post‐thymically would be rendered tolerant of that antigen, and if so whether the mechanism of tolerance induction would differ from that found for thymic antigens. We constructed bone marrow radiation chimeras which were grafted with two thymus lobes differing in minor histocompatibility antigens. T cells which matured in one thymus would be tolerized to the minor histocompatibility antigens expressed in that thymus but would not encounter, and would therefore have no early opportunity of being tolerized to the minor histocompatibility antigens expressed by the other thymus. The initial encounter with the minor antigens on the second thymus would occur post‐thymically. Would these T cells be tolerant or responsive to those minor histocompatibility antigens? We found that tolerance was dominant in these chimeras. The data further suggest that the mechanism responsible for tolerance induction in the periphery may differ from that which operates in the thymus.
Different mechanisms account for the suppression of interleukin 2 production and the suppression of interleukin 2 receptor expression in Trypanosoma brucei‐infected mice
Authors: Sileghem Maarten , Darji Ayub , Remels Linda , Hamers Raymond , Baetselier Patrick De 
Published: March 2007

AbstractLymph node cell populations derived from Trypanosoma brucei‐infected mice fail to produce interleukin 2 (IL 2) in response to a potent mitogenic trigger and suppress the potential of normal lymph node cells to secrete IL 2 in co‐culture assays. This suppression is promptly restored by the addition of indomethacin, which blocks prostaglandin synthesis, but is not markedly affected by the addition of catalase, which degrades H2O2. The suppression of the IL 2 receptor expression, on the other hand, is not restored by the addition of indomethacin, nor by the simultaneous supply of both indomethacin and catalase. This discrepancy is not caused by an extreme susceptibility of the receptor expression to low prostaglandin (PG) concentrations, but rather by the presence of suppressive cells that operate through a PG‐independent mechanism. This suppressive mechanism accounts for the loss of the IL 2 receptors on both the Ly‐2 and the L3T4 T cell compartment. The indomethacin‐treated co‐cultures, which manifest a normal IL 2 production but lack the IL 2 receptors, manifest an impaired DNA synthesis and contain a decreased number of T cell blasts.
Ki‐1 (CD30) antigen is released by Ki‐1‐positive tumor cells in vitro and in vivo. I. Partial characterization of soluble Ki‐1 antigen and detection of the antigen in cell culture supernatants and in serum by an enzyme‐linked immunosorbent assay
Authors: Josimovic‐Alasevic Olivera , Dürkop Horst , Schwarting Roland , Backé Eva , Stein Harald , Diamantstein Tibor 
Published: March 2007

AbstractAn enzyme‐linked immunosorbent assay (ELISA) has been developed that allows the quantitative determination of the Ki‐1 (CD30) antigen in soluble form. Similar levels of sensitivity of this new Ki‐1 ELISA and the ELISA previously described for measuring the soluble 55‐kDa chain of the interleukin 2 receptor were seen. As assessed with this ELISA, the investigated Ki‐1 permanent cell lines released the Ki‐1 antigen into the culture supernatant. In culture supernatants of concanavalin A‐activated human peripheral blood lymphocytes, however, this antigen could not be detected. The released Ki‐1 antigen has an apparent molecular weight (Mr) of 85000, whereas the cell‐associated Ki‐1 antigen has an Mr of 105000. We investigated sera from 30 normal donors, 15 patients with systemic infections, and 63 patients suffering from lymphomas for soluble Ki‐1 antigen. In all sera from normal donors and patients with systemic infectious diseases, soluble Ki‐1 antigen was below the detection limit (i.e., < 70 pg). In contrast, high amounts of the soluble Ki‐1 antigen were found in sera from 18 malignant lymphomas containing Ki‐1 tumor cells. This finding demonstrates that the release of the Ki‐1 antigen takes place not only in vitro, but in vivo as well. Moreover, these results imply that the Ki‐1 antigen may be used as a serum tumor marker.
Simultaneous production of interleukin 6, interferon‐β and colony‐stimulating activity by fibroblasts after viral and bacterial infection
Authors: Damme Jo Van , Ronald Schaafsma M. , Fibbe Willem E. , Frederik Falkenburg J. H. , Opdenakker Ghislain , Billiau Alfons 
Published: March 2007

AbstractDifferent viruses were compared with the double‐stranded RNA poly(rl)· poly(rC) and interleukin (IL) 1 for their IL 6‐inducing potential in several human and animal cell types. The laboratory viruses Sendai, Mengo and Newcastle disease virus were found to dose dependently stimulate IL 6 production in diploid fibroblasts. A similar effect was obtained with the human pathogens, measles and rubella virus. Concomitantly with IL 6, two other cytokine activities, i.e., interferon‐β and colony‐stimulating activity for granulocytes and monocytes, were induced. In addition, these three activities were also produced by fibroblasts in response to Escherichia coli, whereas lipopolysaccharide was only marginally active. The specificity of the induction phenomenon was confirmed by the lack of IL 6 induction with inactivated infectious agents and by the complete neutralization of produced IL 6 by specific antibodies. This study indicates that the coordinate production of hemopoietic growth factors and interferon, originating from cells that do not classically belong to the immune system, can influence the local and systemic reactions observed during host defence against various infectious agents.
Schwann cells co‐cultured with stimulated T cells and antigen express major histocompatibility complex (MHC) class II determinants without interferon‐γ pretreatment: synergistic effects of interferon‐γ and tumor necrosis factor on MHC class II induction
Authors: Kingston Ann E. , Bergsteinsdottir Kristin , Jessen Kristjan R. , Van Meide Pieter H. Der , Joseph Colston M. , Mirsky Rhona 
Published: March 2007

AbstractSchwann cells (SC) do not express major histocompatibility complex (MHC) class II antigens under normal culture conditions. SC can, however, be induced in vitro to express MHC class II molecules by exposure to high concentrations of interferon‐gamma (IFN‐γ) and can present antigens to antigen‐specific T cell lines. In the present study immunohistochemical labeling showed that most SC (>90%) prepared from rat neonatal sciatic nerves expressed MHC class II molecules when cultured together with mycobacterial antigen and T cells, and as a consequence were able to function as antigen‐presenting cells in lymphoproliferation assays, without requiring pretreatment with IFN‐γ. Antigen or T cells alone were ineffective in stimulating MHC class II expression and induction of class II molecules was MHC restricted, requiring the presence of syngeneic T cells. Addition of monoclonal antibody DB1, directed against IFN‐γ to co‐cultures of SC and T lymphocytes stimulated with antigen, prevented the induction of MHC class II antigen on SC. When SC were incubated with recombinant (r)IFN‐γ alone, up to 50% of SC showed positive labeling for MHC class II antigen. This level of expression was enhanced to > 80% when recombinant tumor necrosis factor (rTNF) was also added. rTNF alone had no effect, and addition of DB1 antibody inhibited the synergistic effects of rTNF on MHC class II expression. The effects of rIL4 were also investigated but neither rIL4 alone nor rIL4 in combination with rIFN‐γ induced MHC class II expression by SC. These results show that in the presence of sensitized T lymphocytes and antigen, SC do not require pretreatment with exogenous rIFN‐γ to express MHC class II antigens and function as antigen‐presenting cells. T cell‐derived TNF and IFN‐γ appear to act as mediators of the T cell‐induced expression of MHC class II by SC.
Functional expression of CD28 on T cell antigen receptor γ/δ‐bearing T lymphocytes
Authors: Testi Roberto , Lanier Lewis L. 
Published: March 2007

AbstractT lymphocytes express a T cell antigen receptor (TcR) complex composed of either an TcR α/β or TcR γ/δ heterodimer in noncovalent association with the CD3 glycoproteins. CD28, a 44‐kDa disulfide‐linked homodimer, is present on the surface of the majority of TcR α/β‐bearing T lymphocytes. Monoclonal antibodies (mAb) directed against CD28 potentiate activation signals delivered through the CD3/TcR α/β complex. Herein, we demonstrate that CD28 is expressed on ∼40%–60% of TcR γ/δ‐bearing T lymphocytes in most donors. Anti‐CD28 mAb substantially augmented proliferative signals delivered through the TcR γ/δ, demonstrating the presence of functional CD28 molecules on TcR γ/δ‐bearing T lymphocytes. The majority of TcR γ/δ thymocytes also expressed CD28.
Mouse strain variation in Ly‐24 (Pgp‐1) expression by peripheral T cells and thymocytes: implications for T cell differentiation
Authors: Lynch Felicity , Ceredig Rhodri 
Published: March 2007

AbstractThe cell surface glycoprotein Ly‐24 has been proposed as a useful marker for the identification of in vivo‐primed T cells. Analysis of Ly‐24 surface expression by T cells from different mouse strains has shown variation in Ly‐24 expression that is not H‐2 linked; however, mice of the Ly‐24.1 allele (e.g. BALB/c) express relatively high amounts, whereas Ly‐24.2 strains (e.g. C57BL/6) are low expressors. In BALB/c (Ly‐24 high) and C57BL/6 (Ly‐24 low) mice, Ly‐24 was expressed by both CD4‐CD8+ and CD4+CD8‐ subpopulations of single‐positive T cells and thymocytes. Among CD4‐CD8‐ thymocytes, the overall expression of Ly‐24 was similar in both mouse strains. Analysis of CD4+ and CD8+ single‐positive thymocytes from newborn and adult BALB/c mice showed that the neonatal population contained fewer Ly‐24+ cells. However, using the cell surface markers J11d and CD3, neonatal single‐positive thymocytes were found to contain larger numbers of cells with the Ly‐24‐J11d+CD3 low to negative phenotype. Taken together, these results show that in BALB/c (Ly‐24 high) mice, as soon as functional mature phenotype (CD3+) CD4+ and CD8+ single‐positive thymocytes are generated, they already express Ly‐24. These data cast doubt on the usefulness of Ly‐24 expression as a universal marker of in vivo‐primed T cells and suggest that in BALB/c mice thymus migrants may well be Ly‐24+. Expression of Ly‐24 by thymocytes is discussed in the context of current models of intrathymic T cell differentiation.
T helper cells grown with hapten‐modified cultured Langerhans' cells produce interleukin 4 and stimulate IgE production by B cells
Authors: Hauser Conrad , Snapper Clifford M. , Ohara Junichi , Paul William E. , Katz Stephen I. 
Published: March 2007

AbstractHapten‐specific CD4 T helper (Th) lines generated by repeated stimulation with hapten‐modified, cultured Langerhans' cells (cLC) release interleukin (IL 4) (B cell stimulatory factor 1) but not detectable IL 2 into the culture media. The growth of Th cells in response to hapten‐modified cLC was inhibited by an anti‐IL 4 monoclonal antibody (mAb) but not by mAb to either IL 2 or the p55 chain of the IL 2 receptor. Furthermore, these cells could be stimulated to proliferate by concanavalin A and IL 1. These results indicate that IL 4 is the autocrine growth factor for these Th lines and that IL 1 plays a critical role in their growth. The Th cells exhibited 1500–10000 high‐affinity IL 4 receptors cell. When cultured with syngeneic, hapten‐modified, small resting B cells, Th cells caused specific IgE production of up to 20 ng/104 B cells. Thus, IL 4 producing Th lines appear to result from their selective stimulation by cLC, suggesting that T cell responses elicited in this way profoundly influence the B cell isotype pattern.
Autoregulation of interleukin 1 production
Authors: Manson Jean C. , Symons Julian A. , Di Glovine Francesco S. , Poole Stephen , Duff Gordon W. 
Published: March 2007

AbstractInterleukin 1 (IL 1) α and β are distinct cytokines with a common receptor on target cells. Both have been implicated in immunity, inflammation and connective tissue metabolism. Their production is stimulated by microbial products and also by other cytokines derived from accessory cells and lymphocytes. Following reports that IL 1 can stimulate its own production, we have tested the effects of recombinant IL 1 on the synthesis and release of IL 1 α and β by human blood mononuclear cells (MNC). We confirmed that autoinduction occurs but report also the novel finding that this effect is very concentration dependent. At some concentrations within the range found in vivo, recombinant IL 1 not only failed to stimulate further IL 1 production but also inhibited the background level of synthesis in 20‐h MNC cultures. The negative feedback appears unrelated to prostaglandin E2 and interferon‐γ levels and could not be reproduced by adding transforming growth factor β. This previously unrecognized autoregulation may be relevant to clinical diseases associated with pathogenic over‐production of IL 1.
Inhibition of cryoprecipitation of murine IgG3 anti‐dinitrophenyl (DNP) monoclonal antibodies by anionic DNP‐amino acid conjugates
Authors: Spertini François , Coulie Pierre G. , Snick Jacques Van , Davidson Eugene , Lambert Paul‐Henri , Izui Shozo 
Published: March 2007

AbstractPreviously we have demonstrated that eight out of nine IgG3 monoclonal antibodies (mAb) obtained from autoimmune MRL‐lpr/lpr mice were able to self‐associate and to precipitate in the cold (Gyotoku et al., J. Immunol. 1987. 138: 3785). To determine whether the cryoprecipitation of IgG3 mAb is enhanced or inhibited in the presence of specific ligand, we have established eight IgG3 mAb reactive with 2,4‐dinitrophenol (DNP) hapten: four mAb were obtained from fusion of spleen cells of C57BL/6 mice immunized with 2,4, 6‐trinitrophenylated keyhole limpet hemocyanin, three from 129/Sv and one from BALB/c immunized with DNP‐lipopolysaccharide. Five of them induced cryoglobulins composed exclusively of the IgG3 mAb. The binding of negatively charged monomeric DNP‐amino acid conjugates completely inhibited the cryoprecipitation of all the five cryoprecipitating anti‐DNP IgG3 mAb, while the incubation with positively charged or neutral DNP‐amino acid conjugates had variable effects: increase, inhibition or no change of the cryoprecipitation. In addition, positively charged DNP‐amino acid conjugates were able to induce the cryoprecipitation of one of the non‐cryoprecipitating anti‐DNP IgG3 mAb. Our data showed that (a) IgG3 mAb derived from non‐autoimmune strains of mice, similar to IgG3 mAb derived from an autoimmune MRL‐lpr/lpr strain, possessed the unique property to self‐associate and were able to form cryoglobulins in most cases; (b) although the Fc‐Fc interactions of IgG3 mAb play a decisive role in IgG3 cold solubility, IgG3 cryoprecipitation was markedly influenced after interacting with their specific ligand, depending on the charge of the hapten‐amino acid conjugate. This suggested that even minor interferences with the electrostatic equilibrium of the IgG3 by the binding of charged hapten molecules induced dramatic changes in the solubility of the IgG3 mAb at low temperature.
Human interleukin 4 down‐regulates the surface expression of CD5 on normal and leukemic B cells
Authors: Defrance Thierry , Vanbervliet BÉAtrice , Durand Isabelle , Banchereau Jacques 
Published: March 2007

AbstractCD5 is a pan‐T cell antigen which is expressed on a minor subset of normal B lymphocytes and on most chronic lymphocytic leukemia B cells (B‐CLL). In this study, it is demonstrated that interleukin (IL) 4 down‐regulates the surface expression of CD5 on tonsil B cells and B‐CLL cells, but not on T cells. IL 4 inhibits both the spontaneous and the phorbol myristate acetate (PMA)‐induced hyperexpression of CD5 on tonsil B cells. In contrast, IL 4 only suppresses the PMA‐induced hyperexpression of CD5 on B‐CLL, whereas the spontaneous CD5 expression is essentially unaffected. The IL 4 concentrations required to down‐regulate CD5 are the same as those required to up‐regulate CD23. The IL 4‐mediated down‐regulation of CD5 is an intrinsic property of this IL, since an anti‐IL 4‐neutralizing antiserum blocks this effect. Interferon (IFN)‐γ, which inhibits the IL 4 induced CD23 expression, does not block the IL 4‐induced down‐regulation of CD5. Recombinant IL lα, IL 2, IL 3, IL 5, IL 6, tumor necrosis factor (TNF)‐α, IFN‐γ and granulocyte macrophage colony‐stimulating factor neither inhibit nor stimulate CD5 expression on B cells, there fore suggesting that the capacity to down‐regulate CD5 expression on B cells is specific to IL 4.
Internalization of interleukin 1 (IL 1) correlates with IL 1‐induced IL 2 receptor expression and IL 2 secretion of EL4 thymoma cells
Authors: Hoegen Ilka Von , Falk Werner , Kojouharoff Georgi , Krammer Peter H. 
Published: March 2007

AbstractThe cytokine interleukin 1 (IL 1) plays an important role in the induction of IL 2 secretion and high‐affinity IL 2 receptor (IL 2R) expression by T cells. The events that follow binding of IL 1 to IL 1R, however, are still unknown. In this study we describe two variants of the murine thymoma EL4 (5D3 and D6/76) that express comparable numbers of cell surface IL 1 receptors and bind IL 1 with the same affinity, but show distinct IL 1‐dependent IL 2 secretion and IL 2R expression. In the presence of the tumor promoter phorbol 12‐myristate 13‐acetate IL 1 augments IL 2 secretion and IL 2R expression of EL4 5D3 but not of EL4 D6/76 cells. Comparison of the internalization of IL 1 by both clones revealed that EL4 D6/76 was unable to transport cell surface‐bound IL 1 to the cytoplasm. These findings suggest that internalization of receptor‐bound IL 1 is required for the action of this cytokine.