bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triggering CD 28 molecules synergize with CD 2 (T11.1 and T11,2)‐mediated T cell activation
Authors: Pierrès Anne , Lopez Marc , Cerdan Chantal , Nunes Jacques , Olive Daniel , Mawas Claude 
Published: March 2007

AbstractPairs of monoclonal antibodies (mAb) defining epitopes T11.1 and T11.2 on the CD 2 molecule are mitogenic for purified human T cells in the presence of a sub‐mitogenic dose of 12‐O‐tetradecanoylphorbol 13‐acetate (TPA). Anti‐CD 28 mAb can substitute for the action of TPA in the anti‐CD 2‐induced proliferative response of resting T cells, whereas each signal alone is unable to mediate this effect. Co‐stimulation by anti‐CD 2 plus anti‐CD 28 mAb is monocyte independent and besides resting T cells also induces strong proliferation of thymocytes and pre‐activated T cells. Modulation of the CD 3‐T cell receptor complex does not inhibit the co‐stimulatory effects of anti‐CD 2 plus anti‐CD 28 mAb. The effect is largely dependent on endogenously produced interleukin 2, since the response is strongly inhibited in the presence of mAb against the 55‐kDa interleukin 2 receptor chain.
Role of the 2H4 molecule in the activation of suppressor inducer function
Authors: Morimoto Chikao , Matsuyama Takami , Rudd Christopher E. , Forsgren Arne , Letvin Norman L. , Schlossman Stuart F. 
Published: March 2007

AbstractThe monoclonal antibody anti‐2H4 recognizes a 220‐kDa and 200‐kDa glycoprotein and subdivides T4+ cells into distinct subpopulations: the T4+2H4+ inducer of suppression and the T4+2H4− inducer of help. The T4+2H4+ subset has been shown to play a crucial role in the activation of T8+ suppressor cells. In the present study, we attempted to determine whether the 2H4 molecule itself may be involved in initial triggering of suppressor inducer function. The results show that the addition of anti‐2H4 antibody to a mixture of B and T cells resulted in a marked suppression of pokeweed mitogen‐driven Ig synthesis. When anti‐2H4 was added to B cell cultures containing T4+2H4+ or T4+2H4‐ cells but lacking T8 cells, no suppression was generated. In addition to the requirement for T8 cells, no suppression was generated if T4+2H4+ cells were absent. These results suggest that the anti‐2H4 antibody contributes to the activation of the T4+2H4+ lymphocyte subset, which in turn induces T8 cells to suppress B cell Ig synthesis. Biochemical analysis of the T4+2H4+ subset of lymphocytes indicated that the in vitro addition of anti‐2H4 antibody resulted in an increased expression of the 220‐kDa and 200‐kDa structure on T4 cells. We conclude that perturbation of the 2H4 molecule may potentiate the activation of the suppressor inducer subset and that the T200 molecule may be directly involved in suppressor inducer function.
The complement subcomponent C1q mediates binding of immune complexes and aggregates to endothelial cells in vitro
Authors: Daha Mohamed R. , Miltenburg André M. M. , Hiemstra Pieter S. , Klar‐Mohamad Ngaisah , Es Leendert A.Van , Hinsbergh Victor W. M.Van 
Published: March 2007

AbstractThe present studies were initiated to investigate whether soluble immune complexes, upon interaction with complement, can bind to endothelial cells. Human umbilical vein endothelial cells (HUVE) were incubated with purified human125I‐1abeled C1q at 4°C in RPMI‐0.5% bovine serum albumin and assayed for binding. Optimal binding of1251‐labeled C1q to HUVE was reached within 2 h, and saturation of binding was found at concentrations of 5 μg/well input. The binding of125I‐labeled C1q was inhibitable with unlabeled C1q and by the collagenous region of pepsin‐cleaved C1q. No inhibition was observed with the globular heads of C1q, suggesting that C1q binds to HUVE via the collagenous region of C1q.When HUVE were first reacted with various concentrations of C1q, washed and subsequently incubated with125I‐labeled aggregated human IgM (AIgM), binding of125I‐labeled AIgM to HUVE occurred depending on the dose of C1q. Only those aggregates of IgM which react with C1q in a solid‐phase C1q binding assay were able to bind to HUVE presensitized with C1q. In addition it was shown that C1q mediated binding of aggregated IgG to HUVE. Furthermore, immune complexes (IC), that were prepared with bovine thyroglobulin (BTg) and rabbit anti‐BTg, bound to C1q‐preincubated HUVE. These studies suggest that localization of IC on endothelium can be enhanced following interaction of the IC with complement.
Further evidence for a sequentially ordered activation of T cell rearranging gamma genes during T lymphocyte differentiation
Authors: Triebel Frédéric , Lefranc Marie‐Paule , Hercend Thierry 
Published: March 2007

AbstractRecently, we have shown that the majority of human peripheral lymphocytes with a T cell receptor (TcR) γ/δ receptor use a unique gamma chain recognized by the anti‐TigammaA monoclonal antibody. This predominantly expressed gamma protein is encoded by a rearranged gene where the V9 segment has joined the JP segment located upstream of the Cγ1 region (TRGC1). Peripheral TigammaA+ cells were further studied here to shed light on the relation between the two types of TRG rearrangements namely those involving the first (TRG1) vs. the second (TRG2) J‐C region. Thirteen clones reactive with anti‐TigammaA were tested; it was found that the second TRG allele (i.e., the one which does not involve V9‐JP) of these cells was either in germ‐line configuration or, more frequently, rearranged with a downstream V, gene joined to a J segment of the TRG1 region. These data suggest that productive rearrangements on TRG1 leading to the production of a surface‐expressed y chain occur before rearrangements involving the TRG2 region. It supports the view that TRG genes are subjected to a sequentially ordered activation during the process of T lymphocyte differentiation.
Differentiation of thymocytes in fetal organ culture: lack of evidence for the functional role of the interleukin 2 receptor expressed by prothymocytes
Authors: Plum Jean , Smedt Magda De 
Published: March 2007

AbstractThymic rudiments of 14‐day‐old mouse embryos were put into organ culture in the presence of interleukin 2 (IL2) and PC.61, a monoclonal antibody that binds to the IL2 receptor (IL2R). After 5 and 7 days of culture, we found no influence of PC.61 on the growth of the thymus and the composition of the thymocyte subpopulations as studied with a panel of monoclonal antibodies. High‐dose IL 2 treatment of the organ culture resulted in a reduction of the number of thymocytes and a decrease in the single CD4+ and CD4+CD8+ thymocytes, whereas the number of CD8+Ly‐1+ thymocytes and the number of CD4−CD8−Ly−1− IL2R+ thymocytes increased. The effect of high‐dose IL2 treatment was ascribed to the induction of a nonspecific LAK activity. Our findings argue against a functional role of IL2R on prothymocytes during early T cell development.
The progression of the inflammation in established collagen‐induced arthritis can be altered by treatments with immunological or pharmacological agents which inhibit T cell activities
Authors: Hom Joanne T. , Butler Larry D. , Riedl Pamela E. , Bendele Alison M. 
Published: March 2007

AbstractAlterations in the progression of the inflammatory disease in mice with established collagen‐induced arthritis (CIA) by in vivo treatments with either anti‐T cell antibodies or an immunosuppressive drug, whose main targets of action are T cells, were studied. It was demonstrated that the in vivo administration of either monoclonal anti‐L3T4, anti‐Ly‐2 or the combination of anti‐L3T4 and anti‐Ly‐2 failed to modify the inflammatory disease after the arthritis had been initiated. Nevertheless, the progression of disease was decreased by treatments with rabbit anti‐mouse lymphocyte sera (ALS) in mice with established CIA. While there was a substantial reduction in the proliferative responses to the T cell mitogen concanavalin A (Con A) in these ALS‐treated mice, proliferation to a B cell mitogen, lipopolysaccharide, was unaffected. Furthermore, treatments with anti‐Thy‐1.2 monoclonal antibody (mAb) by itself did not alter the progression of the ongoing inflammatory disease, but combined treatments with both anti‐Thy‐1.2 and anti‐L3T4 mAb prevented the further advancement of the arthritic disease. Although mice receiving either anti‐Thy‐1.2 alone or both anti‐Thy‐1.2 and anti‐L3T4 exhibited complete absence of Thy‐1+ cells within their inguinal lymph nodes, the proliferative responses to Con A by LN cells from mice treated with the combination of anti‐Thy‐1.2 and anti‐L3T4 were drastically reduced compared to the responses of either the anti‐Thy‐1.2 or anti‐13T4‐treated groups. Finally, daily treatments with cyclosporin A, an immunosuppressive drug which preferentially acts on T cells, were also effective in modifying the clinical course of the arthritic disease in mice with established CIA. These results suggest that immunocompetent cells which express the Thy‐1 surface marker, most likely Thy‐1+ T cells, may play a role in maintaining and perpetuating the inflammatory disease of established CIA.
Immunoglobulin synthesis in the human myeloma cell line U‐266; expression of two immunoglobulin heavy chain isotypes (ϵ and α) after long‐term cultivation in vitro
Authors: Hellman Lars , Josephson Staffan , Jernberg Helena , Nilsson Kenneth , Pettersson Uif 
Published: March 2007

AbstractA human IgE‐producing myeloma has been cultivated in vitro as a continuous cell line (U‐266) since 1968. Analysis of immunoglobulin production during early passages of the cell line demonstrated a high synthesis rate of monoclonal IgE. Analysis of late passages, cultivated after 1980, revealed a 3‐6‐fold lower rate of IgE secretion, This decrease was accompanied by the appearance of small amounts of IgA in the culture medium together with IgE. RNA was extracted from a late passage of U‐266 and analyzed by Northern blotting, using ϵ and α‐specific oligonucleotides as hybridization probes. The results showed the presence of ϵ as well as α‐specific mRNA. Moreover the results demonstrated that the latter mRNA was derived from the α2 locus and that the ϵ and the α2‐specific mRNA contained the same V region sequences. Southern blot analysis of DNA from the late passage of the U‐266 cell line failed to reveal a recombinatory switch from the ϵ locus to the α2 locus. The expression of α2 is thus likely to be caused by differential splicing rather than by an isotype switch at the DNA level.
Uptake of extracellular Ca2+ and not recruitment from internal stores is essential for T lymphocyte proliferation
Authors: Gelfand Erwin W. , Cheung Roy K. , Mills Gordon B. , Grinstein Sergio 
Published: March 2007

AbstractChanges in free cytosolic calcium concentrations ([Ca2+]i]are thought to be important initiating events in the activation of T lymphocytes. Mitogen‐induced increases in [Ca2+Ii may result from net influx across the plasma membrane and/or release of Ca2+ from intracellular stores. In human T lymphocytes loaded with the fluorescent indicator indo‐1, addition of phytohemagglutinin (PHA) or the anti‐CD3 antibody UCHT‐1 elicits a biphasic [Ca2+]i response. A major component of the initial transient peak was due to release from internal stores whereas the lower plateau phase was sustained by Ca2+ influx. Previous work suggested that Ca2+ influx is essential for interleukin 2 (IL2) secretion and cell proliferation. To determine the relative effects of the initial and sustained phases of [Ca2+]i change, IL2 secretion and cell proliferation, we introduced into the cell 1, 2‐bis(o‐aminophenoxy)ethane‐N,N,N′,N′‐tet‐raacetic acid (BAFTA), a high affinity intracellular Ca2+ chelator which neither contributes to nor interferes with the fluorescence determinations of [Ca2+]i In cells preloaded with BAPTA, both PHA and UCHT‐1 antibody failed to elicit the transient [Ca2+]i overshoot. Only the plateau phase could be observed in the presence of extracellular Ca2+. In contrast, BAPTA‐loaded cells were found to be fully functional when assessed for IL2 receptor expression, IL2 secretion and cell proliferation. Thus, the mitogen‐induced, maximal but transient increase in [Ca2+]i, contributed to mainly by release of Ca2+ from internal stores, does not appear to be essential for these T cell responses.
Interleukin 5 enhances interleukin 4‐induced IgE production by normal human B cells. The role of soluble CD23 antigen
Authors: Pène Jérǒme , Rousset Françoise , Brière Francine , Chrétien Isabelle , Wideman Janus , Bonnefoy Jean Yves , Vries Jan E.De 
Published: March 2007

AbstractInterleukin 4 (IL 4)‐induced IgE production by peripheral blood lymphocytes and tonsil cells from normal donors was enhanced in a dose‐dependent fashion by IL5. IL5 tested alone was not effective. The synergistic effects of IL5 were most pronounced at suboptimal IL4 concentrations, whereas at saturating IL4 concentrations (200‐300 U/ml), IL5 had no effect. Interferon‐γ (IFN‐γ) and F(ab′)2 fragments of monoclonal antibody 25 directed against the CD23 antigen, that blocked IL4‐induced IgE synthesis, also inhibited the production of IgE in the presence of combinations of IL4 and IL5, indicating that IL5 potentiates the activation pathway through which IL4 induces IgE production. In contrast, IL4 (50 U/ml) blocked IL5‐induced IgA synthesis. IL 5 was ineffective in inducing the release of soluble CD23 (sCD23), but in the presence of IL4 an enhanced release of sCD23 was observed, provided IL4 was present at suboptimal concentrations. IFN‐γ completely blocked sCD23 release induced by IL4 and IL5. These results demonstrate that there is a strong quantitative correlation between sCD23 release and induction of IgE synthesis. sCD23 fractionated from the Epstein‐Barr virus‐transformed B cell line RPMI 8866 was ineffective in inducing IgE production. However, sCD23 acted synergistically with suboptimal concentrations of IL4. sCD23 did not modulate the IgE response at saturating concentrations of IL4. Collectively, these data indicate that sCD23 plays an important regulatory role in the modulation of IL4‐induced IgE synthesis mediated by IFN‐y and IL5.
Ly‐6 A/E antigen of murine T cells is associated with a distinct pathway of activation. Requirements for interferon and exogenous interleukin 2
Authors: Toulon Maureen , Palfree Roger G. E. , Palfree Susan , Dumont Francis J. , Hämmerling Ulrich 
Published: March 2007

AbstractThe Ly‐6 pathway of T cell activation was analyzed to identify its essential requirements. Using a monospecific chicken antiserum to Ly‐6E, fully cross‐reactive to its allelic counterpart, Ly‐6A, but unreactive with other members of the Ly‐6 family, we have found that interferon (IFN)‐α/β or γ, Ly‐6 antibody and interleukin 2 (IL2) act synergistically in inducing T cell proliferation. The action of IFN can be attributed to induction of Ly‐6 A/E antigen on T cells, as described previously, and this induction is transcriptionally controlled. Exposure of T cells with elevated Ly‐6 concentrations to chicken anti‐Ly‐6 antibody leads to expression of IL2 receptors. Consequently, the addition of IL2 drives T cell proliferation. Thus, in BALB/c mice the minimum requirements for activation by the Ly‐6 pathway are IFN (as a means of inducing Ly‐6), Ly‐6 antibody (as inducer of IL2 receptors) and IL2. In mice of the Ly‐6. 2 haplotype, IFN is not an absolute requirement. This may be related to the fact that these animals, in contrast to those of Ly‐6.1 haplotype, express Ly‐6 constitutively on a substantial proportion of resting T cells. Thus, T cells of C57BL/6 or DBA/2 mice can be induced to proliferate with Ly‐6 antibody and IL2 alone, although IFN pre‐treatment enhances this response. In BALBic mice the IL2‐driven proliferative response induced through the Ly‐6 pathway occurs selectively in the L3T4− population.
Immunoglobulin diversification in embryonic chicken bursae and in individual bursal follicles
Authors: Lassila Olli , Alanen Anna , Lefkovits Ivan , Cooper Max D. , Pink J.Richard 
Published: March 2007

AbstractPrevious studies have shown that the same immunoglobulin (Ig) Vλ gene (Vλ 1) is rearranged in all chicken B cells, and that extensive sequence diversification of this gene occurs during B cell development in the bursa of Fabricius. We used two‐dimensional gel electrophoresis to compare the heterogeneity of Ig λ light chains produced by B cells at different stages of bursal development. Somatically diversified light chains were observed in Ig molecules produced by bursal cells as early as 15 days of embryonic incubation. The two principal species of light chain observed probably represent glycosylated and nonglycosylated forms of λ chain encoded by alleles of a single λ gene. Extensive diversification was observed during late embryogenesis. We also studied λ light chain diversity in cyclophosphamide‐treated birds repopulated with normal bursal cells. In these birds, individual bursal follicles are repopulated by single B cell precursors. Follicular cells derived from single B cell precursors were able to produce a spectrum of light chains almost as diverse as that of the total bursal cell population. We used two monoclonal anti‐idiotype antibodies to study idiotype expression in individual normal or reconstituted follicles. About 30% of follicles contained 0.1% to 5% of lymphocytes which reacted with one or both of the antibodies. The results indicate that within individual bursal follicles bursa stem cells undergo Ig hyperdiversification.
Establishment of an interleukin 6 (IL 6)/B cell stimulatory factor 2‐dependent cell line and preparation of anti‐IL 6 monoclonal antibodies
Authors: Matsuda Tadashi , And Toshio Hirano , Kishimoto Tadamitsu 
Published: March 2007

AbstractMurine hybridomas producing monoclonal antibodies (mAb) specific to human interleukin 6 (IL6/BSF‐2) were established. One of these hybridomas (MH60.BSF2) was found to be dependent on IL6 for its in vitro growth. None of the known biological factors tested, such as recombinant (r) human (Hu) Illα, rHuILlα, rHuIL2, rHuIL3, rHuIL4, rHu interferon (1FN)‐γ, HuIFN‐β, rHuG‐CSF, or recombinant murine (Mu) IL3, MuIL4, rMuIL5, could induce the in vitro growth of MH60.BSF2 cells. The half‐maximum tritiated thymidine uptake by MH60.BSF2 cells could be achieved by picogram amounts of rIL 6, making this hybridoma clone an indicator cell for specific and sensitive detection of the IL6 activity in test samples. The MH166.BSF2 clone was found to produce IgGl,χ type mAb (αBSF2‐166) capable of neutralizing IL6 activity. The other clone, MH60.BSF2, produced IgM,x type mAb (aBSF2‐60) unable to neutralize IL6 activity. Both mAb specifically reacted with IL6 as demonstrated by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis and Western blotting analysis. An enzyme‐linked immunosorbent assay (ELISA) utilizing αBSF2‐166 and rabbit anti‐IL 6 antibodies was established which could detect as low as 50 pg/ml of IL6. Since both the ELISA and MH60.BSF2 hybridoma could detect small amounts of IL6 in biological fluids, they constitute powerful tools in exploring the presence or the role of IL6 in various immunological disorders.
Interleukin 6 is involved in interleukin 1‐induced activities
Authors: Helle Maarten , Brakenhoff Just P. J. , Groot Els R.De , Aarden Lucien A. 
Published: March 2007

AbstractHuman monocytes produce a number of soluble mediators involved in regulation of inflammation and lymphocyte growth and differentiation such as interleukin 1 (IL1) and tumor necrosis factor. Recently, the cDNA of another monocyte‐derived factor, interleukin 6 (IL6), was cloned. Herein we show that purified E. coli‐derived recombinant IL6 (rIL6) is as active as IL 1 in the thymocyte assay. In addition, IL 1 and IL 6 synergize strongly in stimulating thymocyte proliferation. Another property shared by IL 1 and IL6 is their pyrogenicity. Human rIL6 induces a monophasic fever after i.v. injection into rabbits. Together with the observation that IL 1 induces IL6 in a variety of cells including thymocytes, our data suggest that IL6 is involved in many of the pleiotropic effects of IL1.
Induction of T cell receptor γ chain transcription in murine T cells by trans‐complementation
Authors: Marolleau Jean‐Pierre , Cazenave Pierre‐André , Primi Daniele 
Published: March 2007

AbstractAs an initial approach to understanding the molecular basis of the developmentally regulated expression of T cell receptor (TcR) genes, we constructed hybrids among T cell clones that differ in their expression of CD4 and CD8 antigens as well as in α,β and γmRNA levels. Here we report that the TcRγ gene becomes transcriptionally active in hybrid cells formed between parental clones that lack TcR γ mRNA. We also observed negative trans‐regulation of TcR β but not of TcR α transcription in one of these hybrids. Positive TcR γ transcription was observed both with (CD4−CD8− × CD4−CD8‐) and (CD4−CD8− × CD4+CD8+) hybrids while negative TcRβ gene regulation was only detected in (CD4−TD8‐ × CD4+CD8+) cells. These data suggest that the regulation of TcR α, β and γ genes is mediated by the action of specific transacting factors that become asynchronously active in the various stages of T cell development.
Development of autoreactive L3T4+ T cells from double‐negative (L3T4−/Ly‐2−) Thy‐1+ spleen cells of normal mice
Authors: Reimann JÖRg , Bellan Astrid , Conradt Peter 
Published: March 2007

AbstractThy‐l+/L3T4−/Ly‐2− spleen cells were purified from normal C57BL/6 (B6) and C.B‐17 mice. Cells within this subset expressed the T cell receptor (TcR) for antigen: the majority of cells in this subset were CD3+; a fraction of the cells was stained with the monoclonal antibody (mAb) F23.1; and the TcR molecule was immunoprecipitable with mAb F23.1 from cells within this subset. In limiting dilution analyses, about 1/30 cells within this subset were growth inducible in vitro by stimulation with phorbol myristate acetate (PMA) plus ionomycin; conditioned media containing interleukin (IL)1, IL2, IL3 or IL4 activity neither triggered nor promoted in vitro growth of these cells. The in vitro generated T cells displayed the Thy‐l+/L3T4+/Ly‐2− surface phenotype and were self‐reactive, i.e., proliferated preferentially in response to syngeneic stimulator cells, and secreted IL2 and IL3 only in response to syngeneic but not allogeneic stimulator cells. The proliferative response of these cells to syngeneic stimulator cells was blocked by anti‐self Ia mAb. This autoreactive helper T cell subset was not inducible in purified Thy‐1+ spleen cell subsets from athymic nude mice or scid mice. Autoreactive helper T cells did not express detectable levels of the IL2 receptor (IL2R), and their proliferative response was not blocked by anti‐IL2R mAb. From PMA plus ionomycin‐stimulated double‐negative Thy‐l+ spleen cells, 14 T cell clones were established in long‐term culture which displayed the CD3+CD4+CD8− surface phenotype and were self‐reactive.
On the structure of polymeric IgM
Authors: Davis Ann C. , Roux Kenneth H. , Shulman Marc J. 
Published: March 2007

AbstractThe cysteine at position 575 of the immunoglobulin μ heavy chain is thought to provide the only disulfide bonds joining the monomer subunits of mouse polymeric IgM. The importance of this cysteine in the assembly of polymeric IgM was investigated by using site‐directed mutagenesis to produce μ chains with serine at position 575. Thirty percent of the secreted mutant IgM was covalently assembled polymer implying that cysteines other than Cys575 can form inter‐subunit disulfide bonds. The polymeric IgM lacked J chain, mediated complement‐dependent cytolysis and appeared to have a higher molecular weight than conventional IgM pentamers, as judged by sucrose gradient sedimentation and sodium dodecyl sulfate‐polyacrylamide gel electrophoresis mobility. Electron microscopy revealed that the mutant IgM molecule contained six subunits.Wild‐type IgM, while synthesized predominantly as a pentameric molecule, was assembled in at least two other forms, which were distinguished by their electrophoretic mobility. The apparently higher molecular weight forms of wild‐type IgM include hexameric molecules which, like the hexameric mutant IgM, contained much less J chain that the pentameric form and were 20‐fold more efficient at activating complement‐dependent cytolysis.