摘要:

AbstractThe expression of CD40 ligand (CD40L) on activated T cells (CD4+T cell clone MT9) is diminished when the T cells are cultured in the presence of B cells. This effect, observed both with normal tonsil B cells and with the B cell line JY, was detected after 6 h and sustained at least until 18 h of co‐culture. Analysis of mRNA showed that CD40L mRNA levels were not modified after 6 h, but were significantly down‐regulated after 18 h of co‐culture with B cells. Although CD40L expression could not be detected by a CD40‐Fc chimera, the molecule was still expressed at the membrane as shown with a polyclonal antiserum against CD40L (anti‐TRAP). In addition, T cells activated in the presence of B cells were stained by a polyclonal antiserum against CD40, without the appearance of CD40 mRNA. These results indicated that a soluble form of CD40 (sCD40) bound to the expressed CD40L on T cells. The existence of sCD40 was confirmed by detection of sCD40 in B cell supernatants using a specific enzyme‐linked immunosorbent assay. Collectively, these data show that B cells can regulate the expression of CD40L on activated T cells at least by two different

ISSN:0014-2980    

DOI:10.1002/eji.1830240402

出版商:WILEY‐VCH Verlag GmbH    

年代:1994

数据来源: WILEY

摘要:

AbstractIt was observedin vitroandin vivothat both interferon (IFN)‐γ and interleukin (IL)‐12 can promote the development of T helper type 1 (TH1) cells. Since IL‐12 was shown to be a costimulator for the production of IFN‐γ by T or natural killer (NK) cells, IL‐12 might play only an indirect role in TH1 differentiation by providing IFN‐γ which represents the essential differentiation factor. Using anti‐CD3 monoclonal antibody (mAb) for activation of naive CD4+T cells in the absence of accessory cells we could demonstrate that costimulation by IFN‐γ alone results only in marginal TH1 development. Similarly, IL‐12 in the absence of IFN‐γ is only a poor costimulator for inducing differentiation towards the TH1 phenotype. Our data indicate that both cytokines are required to allow optimal TH1 development and that IL‐12 has a dual role, it promotes differentiation by direct costimulation of the T cells and also enhances the production of IFN‐γ which serves as a second costimulator by an autocrine mechanism. Another cytokine that was reported to favor TH1 differentiation in certain experimental systems is transforming growth factor (TGF)‐β. With naive CD4+T cells employed in this study TGF‐β strongly inhibited the production of IFN‐γ triggered by IL‐12 as well as the IL‐12‐induced TH1 development. When TGF‐β was combined with anti‐IFN‐γ mAb for neutralization of endogenous IFN‐γ the TH

ISSN:0014-2980    

DOI:10.1002/eji.1830240403

出版商:WILEY‐VCH Verlag GmbH    

年代:1994

数据来源: WILEY

摘要:

AbstractT cell from H‐2bmice recognize at least 12 sequence regions on theTorpedoacetylcholine receptor (TAChR) α, γ and δ subunits. Immunization of C57BL/6 mice with individual synthetic TAChR sequences known to contain CD4+epitopes resulted in most cases (10 out of 12 peptides) in anti‐peptide antibody (Ab) production, indicating that short TAChR sequences contain both CD4+and B epitopes.Immunization of C57BL/6 mice with a mixture of a CD4+epitope peptide, from the TAChR or from an unrelated protein, plus another TAChR sequence forming a “pure” B epitope (Tα63–80), induced in most cases anti‐peptide Ab and CD4+cell sensitization only against the peptide containing the CD4+epitope. However, when the T epitope peptide Tα360–378 was co‐injected with the B epitope, Ab were also produced against the B epitope peptide. Injection of the individual peptides Tα360–378 and Tα63–80 at different and distant sites along the back of mice elicited sensitization of CD4+cells and Ab production only against peptide Tα360–378.Therefore, when optimal cooperation between T and B cells occurs, spatial proximity but not covalent association of the B and the CD4+epitope is necessary for productio

ISSN:0014-2980    

DOI:10.1002/eji.1830240404

出版商:WILEY‐VCH Verlag GmbH    

年代:1994

数据来源: WILEY

摘要:

AbstractWe have previously shown, through transfection experiments, that the murine B7 (mB7) molecule, a ligand for the CD28 and CTLA‐4 receptors, is a sufficient costimulatory signal for the antigen‐specific and major histocompatibility complex (MHC)‐restricted activation of murine CD4+T lymphocytes. In addition to mB7, another ligand with affinity for CTLA‐4 has been described on spleen cells. Here we report our studies on the expression and function of these molecules on murine Langerhans cells (LC). Both anti‐mB7 monoclonal antibody (mAb) 16‐10A1 and human CTLA4Ig (hCTLA4Ig), a chimeric fusion protein consisting of the extracellular domain of human CLTA‐4 and the constant domain of human IgG1, detected antigens(s) on cultured but not freshly isolated LC. Preincubation of cultured LC with anti‐mB7 mAb did not significantly affect binding of hCTLA4Ig to these cells. This result demonstrate the existence of at least one other ligand for the CLTA‐4 receptor on cultured LC. Functional studies revealed that the costimulatory activity of LC was inhibited better by hCTLA4Ig than by the anti‐mB7 mAb. This differential effect was seen in the case of both alloreactive and antigen‐specific, syngeneic T cell responses. These findings suggest that the non‐mB7‐ligand for CTLA‐4 is functional and participates in the induction of immune responses by LC. Importantly, even synergistic combinations of anti‐mB7 mAb and hCTLA4Ig did not inhibit completely the activity of LC. These findings therefore raise the possibility that LC express other costimulatory ligands besides m

ISSN:0014-2980    

DOI:10.1002/eji.1830240405

出版商:WILEY‐VCH Verlag GmbH    

年代:1994

数据来源: WILEY

摘要:

AbstractOn human B cells the antigen receptor complex is composed of the membrane form of the immunoglobulin molecule and the non‐covalently associated Igα/β heterodimer. A small subpopulation of normal B cells and chronic lymphocytic leukemia B cells express (analogous to T cells) the transmembrane molecule CD5, a counterstructure of B cell‐specific CD72. Numbers of CD5+B cells are increased in several physiological and pathological conditions. Moreover, CD5+B cells are being held responsible for the production of autoreactive antibodies and seem to have signaling characteristics distinct from conventional B cells. On T cells, CD5 associates with the T cell receptor CD3 complex and ligation of CD5 leads to the generation of co‐stimulatory signals, that act on T cell activation. We here demonstrate that CD5 is associated with the B cell receptor (BCR) complex and serves as substrate for BCR‐induced tyrosine kinase activity. Hence, CD5+B cells have a unique potential to modulate BC

ISSN:0014-2980    

DOI:10.1002/eji.1830240406

出版商:WILEY‐VCH Verlag GmbH    

年代:1994

数据来源: WILEY

摘要:

AbstractThe joining of immunoglobulin gene segments during B cell development consists of a tightly regulated series of rearrangement steps. A variety of experiments have suggested that transcription is involved in activating the locus as substrate for the V(D)J recombinase. Here, we have characterized a region located immediately upstream of the most J‐proximal D element (DQ52), which contains both promoter and enhancer activities preferentially active in precursors of B cells. Interestingly, this DQ52 regulatory element is inevitably deleted in fully rearranged H chain genes. We propose that it is involved in the early activation and rearrangement events at the IgH locu

ISSN:0014-2980    

DOI:10.1002/eji.1830240407

出版商:WILEY‐VCH Verlag GmbH    

年代:1994

数据来源: WILEY

摘要:

AbstractIn this report we demonstrate that murine bone marrow cells cultured in either interleukin (IL)‐3 or mast cell growth factor (MGF, also known as c‐kit ligand and stem cell factor) differentially express cytokine genes. Bone marrow cells cultured in IL‐3 differentiate and proliferate, taking on a mucosal mast cell‐like phenotype. These cells express the IL‐4 gene. Bone marrow cells cultured in MGF take on a connective tissue mast cell‐like phenotype and possess transcripts for both of the subunits of the IL‐12 cytokine. Bone marrow cells cultured in both IL‐3 and MGF express the IL‐4 gene at lower levels than that seen for the IL‐3 culture alone, but do not possess IL‐12 gene transcripts. The level of IL‐12 subunit transcripts derived from the MGF‐derived bone marrow cells was compared to that found in splenocytes and activated macrophages, the only cells in which IL‐12 production has been previously documented. Both of the IL‐12 subunit transcripts were found, compared to a β‐actin control, to be present within MGF‐derived cells in the same if not higher quantities than the splenocyte or macrophage cultures. Mucosal mast cells have been previously implicated in the development of the T helper type 2 (TH2) T cell phenotype via their expression of IL‐4. The finding that the MGF‐derived connective tissue‐like mast cells possess IL‐12 transcripts suggests that the development of the TH1 T cell pathway may be posit

ISSN:0014-2980    

DOI:10.1002/eji.1830240408

出版商:WILEY‐VCH Verlag GmbH    

年代:1994

数据来源: WILEY

摘要:

AbstractFrom the genomic DNA of a single individual, we have amplified, cloned and sequenced 37 human germ‐line Vχsegments. Four of these segments were new. We then compiled a comprehensive directory of all germ‐line Vχsegments and identified 50 different sequences with open reading frames. Comparison with 236 rearranged sequences revealed that no more than 24 of these germ‐line sequences could be assigned rearranged counterparts, that some of these were rarely used, and that only about 11 sequences are used frequently. This suggests that the expressed Vχrepertoire is mainly derived from a limited number of segments. Most surprisingly, the Jχ‐distal region of the locus appears to be rarely used: we could unambiguously assign 162 rearranged sequences to Vχsegments of the Jχ‐proximal region, but only 5 to segments of the J

ISSN:0014-2980    

DOI:10.1002/eji.1830240409

出版商:WILEY‐VCH Verlag GmbH    

年代:1994

数据来源: WILEY

摘要:

AbstractThe distribution of T cells using the Vβ2 gene was studied in a group of 99 humans. The distribution of Vβ2+CD4+levels was bimodal. Twelve individuals had levels of Vβ2+CD4+less than 2% and 86 others had values greater than 5%. Only one individual had a value between 2% and 5%. The Vβ2 low (mean 1.3 ± 0.49) and Vβ high (mean 8.2 ± 1.65) phenotypes were stable. The Vβ low phenotype is inherited and not limited to HLA or T cell receptor Vβ gene complexes. The CD8Vβ2 levels of CD4Vβ2 low individuals are also low. The residual Vβ2+T cells in Vβ2 low individuals were not anergic to Vβ2‐specific stimulation. These data are compatible with the effects of an endogeno

ISSN:0014-2980    

DOI:10.1002/eji.1830240410

出版商:WILEY‐VCH Verlag GmbH    

年代:1994

数据来源: WILEY

摘要:

AbstractInfection withHerpesvirus saimiri, a tumor virus of non‐human primates, transformed human CD4+T cell clones to permanent interleukin (IL)‐2‐dependent growth without need for restimulation with antigen and accessory cells. The IL‐2‐dependent proliferation of these cells was dramatically inhibited by soluble anti‐CD4 whole antibodies, F(ab′)2and Fab fragments, and also by gp 120 of human immunodeficiency virus. The inhibition was not due to cell death and could be overcome by high concentrations of exogenous IL‐2. Cell surface expression of CD4, and to a lesser degree the density of the IL‐2 receptor α chain, were reduced upon anti‐CD4 treatment. After long lasting (>12h) incubation with anti‐CD4, abundance and activity of CD4‐bound p56lckwere diminished while the free fraction of p56lckremained unchanged. Since IL‐2 binding to its receptor activated only the CD4‐bound fraction of p56lck, the IL‐2‐induced p56lckactivity was diminished after long‐term CD4 ligation. Taken together, our results suggest a cross talk between CD4‐ and IL‐2

ISSN:0014-2980    

DOI:10.1002/eji.1830240411

出版商:WILEY‐VCH Verlag GmbH    

年代:1994

数据来源: WILEY