bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD23/CD21 interaction is required for presentation of soluble protein antigen by lymphoblastoid B cell lines to specific CD4+ T cell clones
Authors: Grosjean Isabelle , Lachaux Alain , Bella Chantal , Aubry Jean‐Pierre , Bonnefoy Jean‐Yves , Kaiserlian Dominique 
Published: March 2007

AbstractPrevious studies have documented a role for membrane‐bound CD23 (the low affinity FcεRII) in presentation of alloantigens by B cells. The aim of the present study was to examine the involvement of cell surface CD23 in presentation of more conventional soluble protein antigens to T cells. We show that antibodies to CD23 and to its lymphocyte‐associated second ligand, CD21, inhibit presentation of the cow's milk allergen casein, by autologous CD23+CD21+ B‐EBV cell lines to casein‐specific HLA‐DP‐restricted CD4+ T cell clones obtained from patients with either reaginic or enterophatic forms of cow's milk protein intolerance. Maximal inhibition was achieved when the antibodies were added at the initiation of the culture. The absence of specific inhibition by an anti‐DRα monoclonal antibody (mAb) argues against a steric hindrance phenomenon impeding access of the T cell receptor to major histocompatibility complex class II molecules. Rather, anti‐CD23 and anti‐CD21 mAb‐induced inhibition of antigen presentation seems to affect at least partly, heterotypic conjugate formation through CD23/CD21 interaction. Double immunofluorescence labeling of the T cell clones and antibody inhibition of T/B conjugate formation shows that functional CD23 and CD21 molecules are induced on T cells following contact with B‐EBV cell lines. Taken together, these data indicate that CD23/CD21 interactions between T and B cells are required for presentation of soluble protein antigens by B‐EBV cell lines to specific CD4+ T cells. The potential implications of these findings for allergen‐specific T cell activation are discussed.
The murine interleukin‐2 receptor γ chain gene: Organization, chromosomal localization and expression in the adult thymus
Authors: Disanto James P. , Certain Stéphanie , Wilson Anne , MacDonald H. Robson , Avner Phillip , Fischer Alain , de Saint Basile Geneviève 
Published: March 2007

AbstractDefects in the interleukin‐2 receptor γ (IL‐2Rγ) chain in man result in an X‐linked severe combined immunodeficiency, SCIDX1, characterized by an absence of T‐cell differentiation. This phenotype may result from pertubations in IL‐2‐, IL‐4‐, IL‐7‐ or IL‐15‐mediated signaling, as the IL‐2Rγ chain forms an integral component of these receptor systems. We have isolated and characterized cDNA and genomic clones for the murine IL‐2Rγ. The gene(Il2rg)is well conserved between mouse and man with respect to overall structure and size, and contains regions of high conservation in the promoter region as well.Il2rgmaps to mouse X chromosome region 40, in a region of synteny with human Xq12‐13.1. We have also explored the expression of the IL‐2Rγ during thymocyte development. IL‐2Rγ transcripts are detected in the earliest thymocyte precursor cells and persist throughout intrathymic development into the mature peripheral compartment. Genomic clones for the murine IL‐2Rγ will allow for further studies on the regulation and function of this genein vivo.
Only simultaneous blocking of the L‐ and P‐selectin completely inhibits neutrophil migration into mouse peritoneum
Authors: Bosse Roland , Vestweber Dietmar 
Published: March 2007

AbstractWe have examined the inhibitory effect of monoclonal antibodies against mouse P‐, E‐ and L‐selectin on the migration of neutrophils into the chemically inflamed peritoneum of the mouse. For this purpose, monoclonal antibodies were raised against mouse P‐ and E‐selectin, which block cell adhesion. We found that blocking of each selectin alone inhibited neutrophil migration to a similar degree ranging from 63 % to 72 %. Of the three possible combinations of antibodies against two different selectins only the combination of anti‐P‐ and anti‐L‐selectin antibodies caused an essentially complete blockade of neutrophil emigration. Only the effects of these two antibodies were additive, while the effect of anti‐E‐selectin antibodies did not add to the effect of antibodies against P‐ or L‐selectin. Thus, although E‐selectin is involved in neutrophil migration into the inflamed peritoneum of the mouse, it cannot compensate the block of the other two selectins which seem to play the dominant role in this process.
T cell receptor γδ repertoire in HIV‐1‐infected individuals
Authors: Hinz Thomas , Wesch Daniela , Friese Klaus , Reckziegel Anne , Arden Bernhard , Kabelitz Dieter 
Published: March 2007

AbstractWhile Vγ9Vδ2 cells dominate among peripheral blood γδ T cells in healthy adults, the majority of γδ T cells in most HIV‐1‐infected individuals express Vδ1. We asked whether these elevated levels of Vδ1 T cells were due to clonal expansion. Three‐color flow cytometry with monoclonal antibodies against Vγ2/Vγ3/Vγ4, Vγ4 and Vγ9 was used to investigate Vγ usage in 27 patients with elevated numbers of Vδ1 T cells. While the relative proportion of Vγ9 cells among γδ T cells was significantly reduced in HIV‐1+ inviduals (10 ± 11% vs. 80 ± 17%, p < 0.001), the fraction of γδ T cells using Vγ5 or Vγ8 was significantly increased (54 ± 15% vs. 7 ± 11%, p < 0.001). In 1 patient, 76% of the Vδ1 cells expressed Vγ2 or Vγ3, suggesting clonality of the Vδ1 population. In line with this assumption, analysis of the Vδ1‐Jδ junctional regions by reverse transcription‐polymerase chain reaction (RT‐PCR) resulted in products of only one junctional length, as demonstrated by electrophoresis on denaturing gels, and 12 out of 16 (75%) in‐frame junctional sequences were identical in this patient. In other HIV‐1+ patients, RT‐PCR resulted in products of several distinct sizes, also indicating a highly restricted repertoire. After sequencing the Vδ1‐Jδ junctional regions of 3 additional patients, we found repeated but patient‐specific in‐frame junctions accounting for 10–30% of the sequenced clones. However, limited Vδ1‐Jδ junctional diversity was also seen in healthy donors. RT‐PCR products from 10 healthy individuals resulted in distinct bands on denaturing gels. In 1 of them exhibiting a single prominent band, 10 out of 17 (58%) sequenced junctions were identical. Two other healthy donors displayed 2/14 and 5/18 identical junctional sequences, respectively. Taken together, our results reveal significant alterations of Vγ usage in HIV‐1+ patients, while the Vδ1 junctional repertoire is similarly restricted in HIV‐1+ and HIV‐1− individuals. Therefore, these data argue against an obligatory clonal expansion of Vδ1‐expressing cells during HIV‐1 infection.
T cell receptor Vβ8.2 gene germ‐line transcription: An early event of lymphocyte differentiation
Authors: Candéias Serge , Hardy Richard R. , Li Yue Sheng , Staerz Uwe D. 
Published: March 2007

AbstractRearrangement of the T cell antigen receptor (TCR) β chain genes is highly regulated in both a developmental and a tissue‐specific manner. T cell precursors originate from the yolk sac or fetal liver during gestation and from the bone marrow during adulthood. They initiate the recombination of TCR genes primarily during differentiation in the thymus. It has previously been suggested that transcription of immunoglobulin genes in germ‐line configuration is linked to recombination events within these loci. Here, we examine whether germ‐line transcription of TCR variable genes coincides with their rearrangement or whether it marks even earlier stages of T lymphocyte development. During gestation, we found Vβ8.2 germ‐line transcripts in the fetal liver and the fetal thymus, but not in the yolk sac. This transcription precedes Vβ8.2 to DβJβ rearrangement. In adult animals, we found these transcripts in the thymus, the spleen, the liver and the bone marrow. However, in the liver, this transcription is dependent on the presence of mature lymphocytes. This transcription does not happen in non‐lymphoid cells. In the B lymphocyte lineage, Vβ8.2 germ‐line transcripts are detected only in the earliest stages of differentiation (pre‐pro‐ and pro‐B cells), but not in pre‐B cells and mature B lymphocytes. Altogether, our results show that transcription of the unrearranged Vβ8.2 gene is an early event of lymphocyte development, taking place in lymphocyte precursors, long before Vβ8.2 rearrangement.
Peyer's patch CD8+ memory T cells secrete T helper type 1 and type 2 cytokines and provide help for immunoglobulin secretion
Authors: Lagoo Anand S. , Eldridge John H. , Lagoo‐Deenadaylan Sandhya , Black C. Allen , Ridwan Ben U. , Hardy Kenneth J. , McGhee Jerry R. , Beagley Kenneth W. 
Published: March 2007

AbstractAnalysis of cytokine gene expression by reverse transcription‐polymerase chain reaction (RT‐PCR) demonstrated high spontaneous levels of transcripts for multiple cytokines in murine Peyer's patches (PP) compared to spleen and peripheral lymph nodes. This is consistent with the presence of active germinal centers in PP and their continuous exposure to lumenal antigen including bacterial endotoxin. RT‐PCR analysis of cytokine transcripts in purified PP T cell populations revealed the presence of transcripts for interleukin‐4 (IL‐4), IL‐5 and IL‐10 in addition to interferon‐γ (IFN‐γ) in CD8+ cells purified by flow cytometry. The majority of PP CD8+ T cells were also CD45RB10 (MB23G2−), suggesting that these cells were activated/memory cells. CD8+ cells in spleen and mesenteric lymph nodes (MLN) were predominantly CD45RBhi (MB23G2+) consistent with a resting/naive phenotype. PP and MLN CD8+ T cells also secreted IL‐5 and IL‐10 when stimulated with anti‐CD3 monoclonal antibody and when co‐cultured with PP B cells enhanced secretion of both IgG and IgA. These studies suggest that CD8− T cells at mucosal sites secrete T helper type 2 cytokines and can provide functional help for B cells in these tissues.
Recirculation, phenotype and functions of lymphocytes in mice treated with monoclonal antibody MEL‐14
Authors: Lepault Françoise , Gagnerault Marie‐Claude , Faveeuw Christelle , Boitard Christian 
Published: March 2007

AbstractThe effect of a single injection of an antibody against the peripheral lymph node (PLN) homing receptor or L‐selectin (gp90MEL‐14) was studied in vivo in C57BL/6 mice.L‐selectin is known to be rapidly shed from leukocytes in humans and in mice following activation or cross‐linking in vitro. Here we demonstrate that in vivo a single injection of MEL‐14 antibody induces a rapid, almost complete and reversible down‐regulation of L‐selectin expression on both T and B cells. This modulation is dose dependent, specific for L‐selectin and lasts for 10 days. On neutrophils. L‐selectin expression was moderately decreased, and the injected antibody was detectable on the cell surface for several days. Thus, L‐selectin expression after antibody binding in vivo was affected differently on neutrophils and lymphocytes.MEL‐14 treatment induces profound alterations of cell traffic. Loss of L‐selectin on lymphocytes leads to drastic PLN depletion and increased spleen cellularity. Depleted PLN were highly enriched in MEL‐14−/lo, CD44hi and CD11ahi cells, which may represent transiently sessile memory/activated cells.The unresponsiveness in mixed lymphocyte reaction of PLN cells from treated animals and of purified L‐selectin− PLN T cells from normal mice supports this view. However, PLN and spleen cells from treated animals responded normally to non‐antigen‐specific stimuli.
Effect of interferon‐γ on antigen processing in human monocytes
Authors: Nadler Steven G. , Rankin Bruce M. , Moran‐Davis Patty , Cleaveland Jeffrey S. , Kiener Peter A. 
Published: March 2007

AbstractThe effect of interferon‐γ (IFN‐γ) on the ability of human monocytic cells to process exogenous (major histocompability complex class II) antigens was investigated. The processing (i.e. protein degradation) of antigens that were internalized via Fcγ receptor (FcγR) was followed for various times after treatment of cells with IFN‐γ. THP‐1 cells that had been treated with IFN‐γ for 4 h degraded antigen, internalized as an immune complex, at an enhanced rate. After 24 h of IFN‐γ treatment the rate of processing was similar to untreated cells. Unexpectedly, in cells which had been treated for 48–72 h there was a significant decrease in the rate of processing of the exogenous antigen. These effects were not due to changes in the rate of internalization of immune complex. The inhibition of the rate of processing was independent of the type of antigen, was dependent on the dose of IFN‐γ, and also occurred with normal human peripheral monocytes. Analysis of the degraded peptides by high‐pressure liquid chromatography indicated that some of the peptides generated in the IFN‐γ‐treated cells were both quantitatively and qualitatively different from the peptides generated in untreated cells. These data suggest that IFN‐γ modulates the way in which antigens, internalized through Fc receptors as immune complexes, are processed. Additionally, the results imply that decreases in the rate of antigen processing may lead to more efficient antigen presentation.
Role of the CD40‐CD40 ligand interaction in CD4+ T cell contact‐dependent activation of monocyte interleukin‐1 synthesis
Authors: Wagner David H. , Stout Robert D. , Suttles Jill 
Published: March 2007

AbstractMost studies of the induction of cytokine synthesis in monocytes have employed an exogenous triggering agent such as lipopolysaccharide. However, in nonseptic inflammatory responses (e.g. rheumatoid arthritis) monocyte activation occurs as a result of T cell‐generated signals. In previous reports, we and others have demonstrated that contact‐dependent T cell‐generated signals are capable of contributing to macrophage activation. We have shown that plasma membranes from anti‐CD3 activated purified peripheral CD4+ T cells (TmA) but not from resting CD4+ cells (TmR) induce monocytes to synthesize interleukin (IL)‐1 in the absence of co‐stimulatory cytokines. Studies to determine the expression kinetics of the molecule(s) unique to activated CD4+ T cells which interact with monocytes to induce IL‐1 revealed that optimal expression occurred at 6 h post activation. This matched the previously reported kinetics of expression of CD40 ligand (CD40L) on activated peripheral T cells, implicating the CD40‐CD40L interaction as a candidate for the initiator of the IL‐1 signaling event. The ability of TmA to induce IL‐1 synthesis in resting monocytes could be markedly reduced by addition of a monoclonal anti‐CD40L antibody, 5c8. In addition, a monoclonal anti‐CD40 IgM (BL‐C4) proved dramatic in its ability to induce resting monocytes to synthesize IL‐1. In summary, these results demonstrate that the CD40‐CD40L interaction provides a critical component of CD4+ T cell contact‐dependent activation of monocyte IL‐1 synthesis.
Identification of a naturally processed HLA A0201‐restricted viral peptide from cells expressing human papillomavirus type 16 E6 oncoprotein
Authors: Bartholomew Jennifer S. , Stacey Simon N. , Coles Brian , Burt Deborah J. , Arrand John R. , Stern Peter L. 
Published: March 2007

AbstractHuman papillomavirus (HPV) DNA encoding the oncogenic proteins E6 and E7 is usually retained in cervical carcinomas, implicating these proteins as potential target antigens for immune recognition in this virally associated tumor. We have characterized endogenously processed peptides eluted from major histocompatibility complex class I molecules in cells infected with a recombinant vaccinia expressing the HPV‐16 E6 oncoprotein. The reverse‐phase chromatography profile of peptides eluted from isolated HLA‐A0201 molecules in cells expressing the E6 oncoprotein differs from that of cells not expressing E6. Sequential Edman degradation of novel peaks found in the peptide profiles from cells expressing HPV‐16 E6 led to the identification of a naturally processed HLA‐A0201‐restricted E6 peptide of sequence KLPQLCTEL. This approach has allowed the identification of a viral peptide which is processed and presented by cells expressing the E6 oncoprotein and is a likely target for cytotoxic T lymphocyte recognition in HLA‐A0201‐positive patients.
Identification of the core residues of the epitope of a monoclonal antibody raised against glycoprotein D of herpes simplex virus type 1 by screening of a random peptide library
Authors: Schellekens Gerard A. , Lasonder Edwin , Feijlbrief Matty , Koedijk Danny G. A. M. , Drijfhout Jan Wouter , Scheffer Albert‐Jan , Welling‐Wester Sytske , Welling Gjalt W. 
Published: March 2007

AbstractRandom peptide libraries (RPL) displayed on the surface of a filamentous bacteriophage can be used to identify peptide ligands that interact with target molecules. We have used a 15‐amino acid residue RPL displayed on bacteriophage M13 to identify the core residues within the epitope of a monoclonal antibody (mAb) A16 which interacts with a continuous epitope restricted to amino acid residues 9 to 19 in the N‐terminal region of glycoprotein D of herpes simplex virus type 1 (gD‐1). The single peptide sequence obtained after three rounds of selection contained identical residues at three positions compared to the authentic gD‐1 sequence. Synthetic peptides were prepared based on the sequence of the original epitope and the phage‐derived epitope. The binding constants (Ka) with mAb A16 were determined using surface plasmon resonance (SPR) biosensor technology. The RPL‐derived peptide and peptide 9–19 of gD‐1 had approximately the same affinity for mAb A16. This suggests that those residues within the epitope that are essential for binding were identified. The synthesis of shorter versions of the RPL‐derived peptide restricted the binding region to seven amino acid residues. These results show that minimal information retrieved from the screening of an RPL combined with peptide synthesis can characterize the epitope of an mAb with high resolution. Immunization of mice with the phage‐derived peptide protected against a challenge with a lethal dose of herpes simplex virus type 1 equally well as the gD‐1 derived peptide.
Lymphocyte‐activation gene 3/major histocompatibility complex class II interaction modulates the antigenic response of CD4+ T lymphocytes
Authors: Huard Bertrand , Tournier Muriel , Hercend Thierry , Triebel Frédéric , Faure Florence 
Published: March 2007

AbstractThe activation requirements for antigen‐dependent proliferation of CD4+ T cells are well documented, while the events leading to the inactivation phase are poorly understood. Here, we tested the hypothesis that the lymphocyte‐activation gene 3 (LAG‐3), a second major histocompatibility complex (MHC) class II ligand, plays a regulatory role in CD4+ T lymphocyte activation. CD4+ class II‐restricted T cell clones were stimulated by their relevant antigen (hemagglutinin peptide or diphteria toxoid) and antigen‐presenting cells with or without anti‐LAG‐3 monoclonal antibody (mAb). Kinetic studies were performed to monitor different activation parameters, including the measurement of thymidine incorporation, expression of activation antigens and cytokine secretion. Results showed that the time course from the initial time points up to the peak time point was not modified in the presence of anti‐LAG‐3 mAb. However, addition of these antibodies, either as whole IgG or as Fab fragments, led to increased thymidine incorporation values for late time points and, hence, to a shift in the decreasing proliferation curve. We also showed that expression of activation antigens, such as CD25, was higher in the presence of anti‐LAG‐3 mAb, and that cytokine concentrations, i.e. of interferon‐γ or interleukin‐4, were higher in the corresponding culture supernatants. In addition, we tested whether the effects of anti‐LAG‐3 mAb were limited to antigen‐dependent. MHC class II‐restricted responses. The proliferative responses of CD4+ T cell clones following stimulation with either interleukin‐2, mitogens, a combination of anti‐CD2 mAb, immobilized anti‐CD3 or anti‐T cell receptor mAb were not altered by anti‐LAG‐3 mAb. The allogeneic proliferative response of a CD8+ T cell clone was also not affected. Overall, the present analysis reveals a modulating effect of anti‐LAG‐3 mAb, mediated specifically on antigen‐dependent, MHC class II‐restricted responses of CD4+ T cell lines. These results support the view that LAG‐3/MHC class II interaction down‐regulates antigen‐dependent stimulation of CD4+ T lymphocytes.
Properties of mouse CD40. Ligation of CD40 activates B cells via a Ca++‐dependent, FK506‐sensitive pathway
Authors: Klaus Gerry G. B. , Choi Michael S. K. , Holman Mary 
Published: March 2007

AbstractThe immunosuppressive drugs cyclosporine A (CsA) and FK506 selectively abrogate Ca++‐regulated activation pathways in both T cells and B cells. We show here that anti‐CD40‐induced murine B cell proliferation, in the presence or absence of interleukin‐4 (IL‐4) is, like the response to anti‐immunoglobulin (Ig), abrogated by 1–5 ng/ml (concentration causing 50% inhibition ca. 1 nM) FK506. However, the effects of the drug on proliferative responses elicited by anti‐Ig or anti‐CD40 differ significantly: firstly, the response to anti‐CD40 + IL‐4 becomes completely FK506‐resistant within 24 h, whilst that to anti‐Ig remains sensitive significantly longer. Secondly, stimulating B cells concurrently via CD40, surface Ig (sIg) and IL‐4 receptors invokes an FK506‐resistant activation pathway. We previously reported that ligation of either sIg or CD40 receptors, in conjunction with IL‐4, induces the transcription factor, nuclear factor of activated T cells (NF‐AT) in B cells, via a CsA/FK506‐sensitive pathway. However, NF‐AT induction elicited by anti‐Ig/anti‐CD40/IL‐4 is still FK506 sensitive, implying that the drug resistance of the response to these three stimuli involves additional components than NF‐AT. These results indicate that CD40 activates murine B cells via a Ca++‐dependent pathway. In agreement with this, anti‐CD40 induces a modest increase in intracellular Ca++ levels in these cells, which appears to be largely due to Ca++ influx through the plasma membrane.
Interleukin‐8 differentially modulates interleukin‐4‐ and interleukin‐2‐induced human B cell growth
Authors: Kimata Hajime , Lindley Ivan 
Published: March 2007

AbstractThe effect of interleukin‐8 (IL)‐8 on human B cell growth, as determined by thymidine uptake and viable cell numbers was studied. IL‐8 inhibited IL‐4‐induced growth of B cells costimulated with anti‐μ antibodies (Ab) or Staphylococcus aureus Cowan strain I (SAC) in a dose‐dependent fashion. In contrast, IL‐8 did not inhibit IL‐2‐induced growth of B cells. The IL‐8‐mediated inhibition was specific, since it was blocked by anti‐IL‐8 mAb but not by control IgG1. Moreover, anti‐tumor necrosis factor‐α (anti‐TNF‐α) Ab blocked IL‐8‐mediated inhibition. On the other hand, TNF‐α, but not other cytokines including IL‐1β, IL‐3, IL‐5, IL‐6, interferon‐α (IFN‐α) or IFN‐γ, inhibited IL‐4‐mediated growth, and inhibition by TNF‐α was blocked by anti‐TNF‐α Ab but not by control IgG. IL‐4 had no effect on TNF‐α binding by B cells while it decreased TNF‐α production by B cells. IL‐8 had no effect in binding of IL‐4, IL‐2 or TNF‐α by B cells, however, it enhanced TNF‐α production by B cells. These results indicate that IL‐8 inhibited IL‐4‐induced human B cell growth by enhancement of endogenous TNF‐α production.