摘要:

AbstractDendritic cells, isolated from human tonsillar tissue, were found to be potent stimulators of the sodium periodate T cell oxidative mitogenesis reaction. Monoclonal antibodies against CD2, CD4, CD11a, CD18, LFA‐3, ICAM‐1, class I and class II major histocompatibility complex (MHC) inhibited T cell proliferation in this response, whereas antibodies against CD8, CD11b, CD11c and CD16 had no effect. Further, antibodies against CD2, CD11a, CD18, LFA‐3 and ICAM‐1 inhibited the early dendritic cell‐T cell clustering event which occurs in this cell interaction. In contrast, antibodies against CD4, class I and class II MHC did not inhibit clustering. Studies examining the expression of the respective molecules upon isolated dendritic cells and T cells suggest that anti‐LFA‐3 and anti‐class II MHC antibodies inhibit at the level of the dendritic cell, whereas anti‐CD2 and anti‐CD4 antibodies inhibit at the level of the T cell. However, antibodies against CD11a, CD18, ICAM‐1 and class I MHC may inhibit at either or both cell levels.These findings have enabled us to propose a molecular mechanism for dendritic cell‐T cell interaction in oxidative mitogenesis. Dendritic cell‐T cell clustering is mediated by bidirectional binding of LFA‐1 (CD11a and CD18) and ICAM‐1 (involving both molecules on both cell types) and unidirectional binding of CD2 and LFA‐3 (involving T cell CD2 and dendritic cell LFA‐3). This initial event permits a second interaction of dendritic cell and T cell molecules, involving T cell CD4, class I MHC (possibly at both cellular levels) and dendritic cell class II MHC, which del

ISSN:0014-2980    

DOI:10.1002/eji.1830190402

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractSelective expression of CD45 isoforms distinguishes naive and memory T cells in peripheral blood. Paradoxically, although the most recent thymic emigrants are CD45R+CD45 p180−, the majority of thymocytes are CD45 p180+. Speculating that the small subset of thymocytes selectively expressing only the high molecular weight isoforms of CD45 constitute the thymic generative lineage giving rise to peripheral T cells, we characterized the phenotypic and functional properties of CD45 p180−thymocytes. All cells bearing CD45 p180 were removed by rigorous depletion or all CD45R+thymocytes were removed in a parallel depletion. CD45R−thymocytes were essentially the same in phenotype and CD4/CD8 subset distribution as unfractionated thymus, and dissimilar to naive peripheral blood lymphocyte (PBL) T cells. In contrast, CD45 p180−thymocytes, mainly CD45R+, were CD1−CD38−pgp 1+, corresponding closely to the phenotype of naive CD45R+PBL T cells. This subset is enriched in CD4+or CD8+single positives, includes a high proportion of CD4−8−thymocytes which are predominantly CD3−, and appears to have a medullary location. Approximately 40%–50% of CD45 p180−thymocytes expressed a high density of CDw29 (4B4), which in the periphery is expressed at high density only on CD45 p180+memory T cells and at low density on CD45R+naive T cells. However, the expression of high density CDw29 in the absence of CD45 p180 indicates a close resemblance to fetal lymphocytes and suggests an essential role for CDw29 in both the least and the most mature of T cells. If CD45 p180−thymocytes constitute the generative lineage and CD45 p180+cells are commited to intrathymic death, then the CD45 p180−subset should have enhanced proliferative potential. By combining depletion methods with a limiting dilution assay for clonogenic potential, we found that 100% of the clonogenic precursors present in unfractionated thymus were CD45R+CD45 p180−cells. This indicates that the CD45 p180+majority of thymocytes has a very limited capability for proliferation consistent with a commitment to intrathymic death. The clonogenic potential of CD45 p180−thymocytes indicates a greater functional resemblance to PBL T cells than to CD45 p180+thymocytes. In so far as clonogenic potentialin vitroreflects generative potentialin vivo, expression of high molecular weight CD45 isoforms appears to define the generative thymic lineage. Our working hypothesis proposes that expression of CD45 p180 implements the mechanism for eliminating thymocytes with self‐

ISSN:0014-2980    

DOI:10.1002/eji.1830190403

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractIt is well established that a large fraction of murine cytotoxic T cells can recognize allogeneic major histocompatibility complex (MHC) antigens, and that the majority of this response are not restricted by H‐2 antigens of the responding host. In contrast, the murine response against the xenogeneic HLA class I antigens is relatively weak. Moreover, a large proportion of the responding murine T cells do not recognize the HLA antigenper sebut only in an H‐2‐restricted manner, probably as an HLA peptide bound to H‐2.Considerable evidence suggests that in mice the T cell repertoire is selected by thymic H‐2 antigens. Therefore, we asked the question whether in transgenic mice expressing an HLA class I antigen the T cell repertoire would be shaped toward a more effective recognition of other HLA alleles. Normal C57BL/6 (B6) and HLA‐Cw3 ‐transgenic B6 mice were immunized with a B6‐derived cell line transfected with HLA‐A2. The resulting A2‐specific CTL were tested on L cells transfected with either A2 alone, which should identify the H‐2‐unrestricted CTL, and on L cells transfected with A2 plus H‐2bgenes, which should identify the sum of H‐2b‐restricted and unrestricted CTL. Both bulk culture and limiting dilution experiments showed that the CTL precursor frequencies for A2‐specific CTL were not increased in the transgenic mice, and that both strains produced comparable proportions of H‐2b‐restricted and of unrestricted A2‐specific CTL. The B6.Cw3 mice seemed to respond less well to HLA‐A2 than the normal B6 mice, suggesting the possibility of tolerance for peptides shared by the Cw3 and A2 molecules. In conclusion, the T cells in the B6.Cw3 transgenic mice did not seem to be selected towards a stronger and more unrestricted recognition of an allo‐HLA an

ISSN:0014-2980    

DOI:10.1002/eji.1830190404

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractSpontaneous sheep erythrocyte rosette‐forming T cells (T‐sRFC) found in normal mouse spleen are specific for the xenogeneic species of red cells and are distinct from human E rosettes as illustrated by their persistence after sheep red blood cell (SRBC) incubation with anti‐LFA‐3 monoclonal antibodies directed against SRBC molecule binding to the E rosette receptor. We confirm here using monoclonal antibodies that T‐sRFC are Thy‐1+CD3+. Additionally, using cell separation techniques based on panning and cell sorting, it is shown that the vast majority of spleen sRFC have the L3T4−Ly‐2+phenotype. As already shown for anti‐Thy‐1 antibodies, anti‐CD3 and anti‐Ly‐2 antibodies block rosette formation, whereas antibodies to more abundant cell surface antigens (T200, H‐2Db) are not inhibitory. These data suggest that the interaciton of T‐sRFC with SRBC occurs a

ISSN:0014-2980    

DOI:10.1002/eji.1830190405

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractDiabetes in the NOD mouse strain is a genetically programmed T cell‐mediated autoimmune process that is directed against an as yet unknown antigen target(s) on pancreatic β cells. To investigate whether the course of the autoimmune disease could be altered by immune manipulations of the T cell repertoire, we have induced allogeneic tolerance by injecting F1semiallogeneic spleen cells into NOD neonates. This procedure resulted in a significant protection against both insulitis and diabetes. However, although it requires the induction of tolerance, as shown by the failure of non‐tolerizing irradiated cells to prevent autoimmunity, protection appeared to be independent of the major histocompatibility complex haplotypes of the F1spleen cells injected at birth,e.g.(C57BL/6 x NOD)F1, (CBA/Ca x NOD)F1or (BALB/c x NOD)F1cells. In addition, a similar degree of protection was induced, whether the tolerant state, as assessed by mixed lymphocyte reaction studiesin vitro, was of short duration, ∼6 weeks, or lasted for more than 12 weeks. Putative veto or suppressor functions of chimeric T cells were ruled out, since mice tolerized with T cell‐depleted F1spleen cells were equally protected.We conclude that the expression of spontaneous T cell‐mediated autoimmunity can be modulated by immune manipulations at birth. Whether the protection observed in the present experiments resulted from the production of one or several specific holes in the autoimmune T cell repertoire,i.e.cross‐tolerance, or whether it resulted from nonspecific disturbances of the emerging T cell repertoire remains to b

ISSN:0014-2980    

DOI:10.1002/eji.1830190406

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractCD4 T cell clones have been shown to be functionally heterogeneous in the mouse. However, it is not known if normal CD4 T cells are also functionally heterogeneous, or whether functional specialization is a result of cloning and long‐term culture. To approach this question, a monoclonal antibody reacting with a subset of CD4 T cells has been prepared by immunization of rats with different cloned T cell lines all sharing the same functional activity. This monoclonal antibody reacts with a subset of CD45 (T200) molecules by binding to a determinant requiring the expression of the second variable exon of the CD45 molecule. Some CD4 T cells bear high levels of this marker, while others react only weakly. This antibody was used to separate CD4 T cells into two subpopulations. The brightly staining population was found to produce interleukin (IL) 2 and not IL 4, while the weakly staining population produced IL 4 and not IL 2. These data demonstrate that CD 4 T cells in normal mice are already functionally committed, and that they differentially express forms of CD45 that contain the second variable exo

ISSN:0014-2980    

DOI:10.1002/eji.1830190407

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractEven though cyclosporin A (CsA) suppressesin vitroproduction of lymphokines such as interleukin 2 (IL 2) and responsiveness of cytotoxic T cell (CTL) precursors to IL 2, thereby inhibiting thein vitrogeneration of CTL,in vivoCsA does not affect the induction of alloreactive CTL. This paradox suggests that CsA‐resistant signals are operatingin vivo.Using anin vitromodel system in which the requirement for antigen‐presenting cells during primary activation of resting murine CD8 T cells is bypassed by immobilized anti‐CD3 monoclonal antibodies, we here describe conditions in which IL 4 conveys CsA resistance to murine CD8 T cells triggered by immobilized anti‐CD3 monoclonal antibodies to respond to IL 2. CsA resistance of IL 4 and IL 2‐responsive CD8 T cell parallels conditions in which signals provided by IL 4 and IL 2 synergize with each other. CsA dissociatesin vitroproliferative and differentiative events by suppressing the former while enhancing the latter. In addition to the known pleiotropic effects of IL 4, our results define an IL 4‐dependent, CsA‐resistant signal pathway which allows CTL differentiation in the absence of significant cell

ISSN:0014-2980    

DOI:10.1002/eji.1830190408

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractDifferential screening of a subtracted cDNA library led to the detection of two distinct but homologous mouse cDNA, called CTLA‐2α and CTLA‐2β. The corresponding transcripts have a tissue distribution restricted to T lymphocytes, where they are inducible upon activation, and to mast cells. The open‐frame regions of both cDNA encode proteins homologous to cysteine proteinase precursors, remarkably, however, only to the proregion of these. The ctla‐2α and ctla‐β genes both map to the C1 band of mouse chromosome 13. Sequence comparisons suggest that the proregion of an ancestor proteinase gene evolved to the ctla‐2 genes by successive duplications, first to autonomy, then to amplification. These results raise the question of the possible role of cysteine proteinase proregions, of cysteine proteinases themselves and of inhibitors thereof in activated T lymphocytes; from a different point of view, they also show that some protease proregions may have evolved as aut

ISSN:0014-2980    

DOI:10.1002/eji.1830190409

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractHuman T cell rearranging γ genes encode membrane proteins which are expressed by a minor subset of T cells. Extensive studies have shown that TcR γ gene rearrangements result from Vγ‐Jγrecombinations. Here we analyze an unusual rearrangement involving a non‐translatable sequence flanked by heptamer and nonamer signals in a Ti α/β‐positive T cell clone (JF1). This sequence, designated here as IγRS, is distinct from V, D or J elements. It is located in the first intron of the first constant region (Cγ1) and homologous sequences are conserved in Cγ2 introns. In JF1 cells the IγRS is juxtaposed to the Jγ2 segment downstream to a Vγ10‐Jγ1 rearrangement. The use of a cryptic splicing site induced JF1 cells to produce an aberrant large‐sized transcript containing the IγRS 3′ to the first exon of Cγ1. Such a rearrangement occurring downstram to an inframe Vγ‐Jγjunction may induce premature arrest of translation and lack of the C‐terminal part of

ISSN:0014-2980    

DOI:10.1002/eji.1830190410

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY

摘要:

AbstractDonor CD8+T lymphocytes injected into recipient mice incompatible at major histocompatibility complex (MHC) class I genes induce donor‐specific CTL nonresponsiveness, attributed to the veto function of donor cells. Here we show that conditions leading to strong activation of CD4+T cells, namely the presence in the recipient of foreign MHC class II determinants, lead to the apparent loss of veto function of donor cells. This ‘masking’ of veto function is dependent on the dose of foreign MHC class II present. Veto function can be partially restored by treatment of recipientsin vivowith CD4‐specific antibody, a measure which has been shown to eliminate the function of CD4+T cellsin vivo.We conclude that CD4+T cells activated by contact with antigen can interfere with the veto function of CD8+T cells. Consequences of this finding are: (a) veto function of a sample cell population can be overlooked when activation of CD4+T cells occurs simultaneously. (b) The balance between veto function of recipient cells and its abrogation might be responsible for the kind of graft‐vs.‐host reaction generated (CD8+T cell‐mediated and frequently lethal or CD4+T cell‐mediated and not lethal) when parental T cells are injected into recipients incompatible at MHC class I and class II genes, (c) A possible contribution of veto cells should be considered in several protocols in which donor hemopoetic cells were used in conjunction with CD4‐specific antibodies to induce transplantation tolerance, (d) Veto functionin vivodoes not require a contributi

ISSN:0014-2980    

DOI:10.1002/eji.1830190411

出版商:WILEY‐VCH Verlag GmbH    

年代:1989

数据来源: WILEY