摘要:

AbstractImmunization with native type II collagen (CII) of susceptible strains of mice (H‐2q) induces a rheumatoid arthritis‐like disease. Collagen‐induced arthritis (CIA) is an experimental model for T cell‐mediated autoimmune disease. To investigate the T cell receptor (TcR) repertoire involved in the pathogenesis of CIA, CII‐primed DBA/1 mice were treated with various TcR VbT‐specific monoclonal antibodies (mAb) using a protocol resulting in a long‐term elimination of the target T cells.In vivotreatment with anti‐CD4 mAb led to nearly complete protection against CIA. Mice injected with anti‐Vβ8.1,2 or anti‐Vβ5.1,2 mAb had a reduced incidence of arthritis (respectively 28.6% and 50% vs 84.6% for the control group). Administration of anti‐VbT2 mAb delayed the onset of the disease whereas injection of anti‐VbT6 or anti‐VbT11 mAb did not alter CIA. Moreover, the combined treatment with anti‐VbT2 and anti‐Vβ5 mAb efficiently reduced the development of CIA. The humoral response to CII was down‐regulated only in the groups of mice that were improved by the treatment.In vitroproliferative response to CII of lymph node cells from primed DBA/1 was partially blocked by addition of several anti‐VbTmAb. Thus, our findings suggest that the overall T cell response to CII may be polyclonal while the T cell clones involved in the pathogenesis of CIA

ISSN:0014-2980    

DOI:10.1002/eji.1830211202

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractGut‐associated lymphoid tissues (GALT) from aged mice enterically immunized withMycobacterium paratuberculosisprotoplasmic antigen show hyperreactive humoral immune responses; this hyperresponsiveness can be corrected to a considerable extent, but not entirely, by systemic administration of interleukin 2 (IL 2) alone. The aim of the present study was to determine further whether the hyperreactivity in the antigen‐specific humoral immune responses in aged GALT could be fully restored by adoptive transfer ofin vitroexpanded antigen‐specific IL 2‐dependent helper (CD4+VV−) T cells from GALT in conjunction with recombinant IL 2 administration. The results show that the age‐associated hyperresponsiveness in gut mucosal antigen‐specific humoral immune responses can be entirely corrected by adoptive transfer with the antigen‐specific GALT T helper cells together within vivoIL 2 adminstration. The mechanism of this restoration involves reversal of the decline in antigen‐specific CD8+suppressor T cell funct

ISSN:0014-2980    

DOI:10.1002/eji.1830211203

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractThe process of recruitment of leukocytes at sites of inflammation involves direct cell‐to‐cell interactions between leukocytes and vascular endothelial cells (EC) mediated by various adhesion receptors on leukocytes and their inducible endothelial ligands. In this study we have examined the induction on EC of endothelial leukocyte adhesion molecule‐1 (ELAM‐1), intercellular adhesion molecule‐1 (ICAM‐1), and vascular cell adhesion molecule‐1 (VCAM‐1) upon their interaction with subpopulations of human T cells. When co‐cultured with EC both resting CD4+T and CD8+T cells caused a modest increase in the expression of endothelial ICAM‐1. Moreover, resting CD4+but not CD8+T cells induced expression of ELAM‐1 and VCAM‐1 on a small fraction of unstimulated EC. Prior activation with phorbol 12‐myristate 13‐acetate (PMA) significantly increased the ability of T cells to up‐regulate endothelial ICAM‐1 and also induced the expression of both ELAM‐1 and VCAM‐1. PMA‐primed CD4+T cells induced both VCAM‐1 and ELAM‐1 on EC more efficiently than CD8+T cells. Furthermore, the ability to induce the expression of ELAM‐1 and VCAM‐1 was confined to the CD4+CD45R0+memory/primed subpopulation of T cells. This induction of various endothelial adhesion ligands could also be mediated by antigen‐primed CD4+T cell lines. The CD4+T cell‐mediated induction of adhesion ligands required direct intercellular contact with EC because neither cultures of EC and PMA‐primed CD4+T cells separated by a microporous membrane insert nor the conditioned medium of PMA‐primed T cells induced expression of ELAM‐1 and VCAM‐1 on EC. Cyclosporin A significantly inhibited the activation of T cells with PMA but had no effect on the ability of PMA‐primed T cells to up‐regulate endothelial CAM. Thus, CD4+CD45R0+T cells via as yet unknown mechanism can significantly enhance the expression of each of the three endothelial adhesion ligands and, thereby, may facilitate the process of re

ISSN:0014-2980    

DOI:10.1002/eji.1830211204

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractSpecific recognition molecules („homing receptors”︁) on lymphocytes are thought to direct selective entry of cells into different organs. The lectin‐related cell adhesion molecule LECAM‐1 has previously been supposed to mediate lymphocyte entry into peripheral lymph nodes and, partially, mesenteric nodes but not into Peyer's patches. Here we present evidence thatin vivothe molecule is also implicated in homing of mouse lymphocytes to Peyer's patches and may have a more general role as homing receptor for high endothelial venules‐bearing lymphoid tissue, but not for most non‐ly

ISSN:0014-2980    

DOI:10.1002/eji.1830211205

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractWe have isolated thymic stem cells from murine fetal liver using a combination of approaches including discontinuous albumin density gradient separation and anti‐heat‐stable antigen (HSA) antibody plus complement‐mediated lysis. A population of early precursors has been identified which comprises approximately 1% of fetal liver, and which has the capacity to reconstitute alymphoid lobes and give rise to the four thymic subpopulations defined by expression of the T cell differentiation antigens CD4 and CD8. These early precursors express CD44 (Pgp‐1), however, they are negative for expression of Thy‐1, CD4, CD8, CD3, membrane immunoglobulin and HSA cell surface

ISSN:0014-2980    

DOI:10.1002/eji.1830211206

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractRecent evidence has pointed to the mycobacterial 65‐kDa heat‐shock protein (hsp 65) as an antigen that may be important in the pathogenesis of rheumatoid arthritis (RA). Using limiting dilution analysis the frequency of purified protein derivative of tuberculin (PPD) and hsp 65‐responsive T cells was measured in paired peripheral blood and synovial fluid samples of patients with RA. There was no increase in the anti‐PPD or anti‐hsp 65 frequency in synovial fluid compared with peripheral blood. In addition, no difference was found between peripheral blood of RA patients and healthy controls. These results do not support the idea of an important pathogenic role of T cells responding to hsp 65, or a cross‐reacting ant

ISSN:0014-2980    

DOI:10.1002/eji.1830211207

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractThis study was performed as a means to examine the effects of environment and stem cell origin on the molding of T cell receptor gene rearrangements during T cell development. Lethally irradiated adult mice were first reconstituted with (C57BL/6 x DBA/2)F1stem cells, which derived either from a fetal liver or adult bone marrow source. The gene rearrangements in the irradiated thymi were then compared to those in normal fetal or adult thymi by hybridoma analysis. Results showed a general absence of gene rearrangements typical of the normal fetal thymus in both sets of chimeras, α and γ gene rearrangements in chimeric mice matched normal adult patterns. However, chimeric thymocytes were unique in an unusually low frequency of rearrangements at the δ locus. The use of the bone marrowvs.fetal liver as stem cell sources in chimeric mice did not affect the patterns, indicating that environmental factors played a major role in the molding of gene rearrangement at multiple T cell receptor loci. Interestingly, the chromosomal sequence added an additional influence as homologous chromosomes showed allele‐specific rearrangement patterns. We now question whether the unique patterns of rearrangement in irradiated adult thymi may substantially affect developing T cell populations in chimeric animals, particularly with regard to the γ/δ T cell subset. Further analyses are warranted, both in experimental and clinical settings, regarding ultimate potentials for T cell diversity and function in transplantation reci

ISSN:0014-2980    

DOI:10.1002/eji.1830211208

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractTechniques which identify hapten‐specific B cells in tissues have been used to determine the sites of B cell activation in rat spleens in response to T cell‐dependent (TD) antigens and T cell‐independent type‐1 (TI‐1) antigens. Surface‐associated hapten binding by specific memory B cells and. B blasts was distinguished from the strong cytoplasmic hapten binding by specific plasma cells and plasmablasts. Blast cells in S phase were identified in tissue sections by staining cells which had been pulse labeledin vivowith 5‐bromo‐2′‐deoxyuridine.Hapten‐specific B blast cells are found in three sites: (a) around interdigitating cells in the T cell‐rich zones; (b) in the follicular dendritic cell network and (c) in association with macrophages in the red pulp. Hapten‐binding memory B cells, which are not in cell cycle, accumulate in the marginal zones and to a lesser extent the follicular mantles in response to TD and TI‐1 antigens. The hapten‐specific blast response in T zones is confined to the first few days after antigen is given and is low for primary responses to TD antigens, but massive on secondary challenge, when marginal zone memory B cells migrate to the T zones. Both the primary and secondary T zone responses to TI‐1 antigens are impressive and in these responses hapten‐specific B blasts are also found in the splenic red pulp.The follicular response to TD antigens starts with a small number of B blasts (fewer than five) entering each follicle. These increase in number exponentially so that by the 4th day after immunization they fill the follicle. The oligoclonality of the response is shown in simultaneous responses to two haptens where 6%–31% of the follicles on day 3 after immunization contain blasts specific for only one of the two haptens. During the 4th day classical zonal pattern of germinal centers develops. The surface immunoglobulin‐positive B blasts are lost from the follicle center, while one pole of the follicular dendritic cell network fills with surface immunoglobulin‐negative centroblasts. Centroblasts do not increase in numbers but divide to give rise to centrocytes, which re‐express slg and migrate into the follicular dendritic cell network. Cell kinetic studies indicate that the centrocyte population is renewed from centroblasts every 7 h. Centrocytes either leave the germinal center within this time or diein situ.It is probable that the centroblasts and centrocytes are derived from the small number of B blasts which initiate the follicular reaction, for the centrocytes show the same oligoclonality observed at the B blast stage. The germinal center reaction declines gradually and 3 weeks after immunization centroblasts and centrocytes are no longer seen. At this time small clusters of B blasts can be found proliferating in the follicular dendritic cell network. These secondary B blasts characterize the third phase of the follicular reaction, which continues throughout the established phase of TD responses. Some follicular response is seen to TI‐1 antigens but this is much less

ISSN:0014-2980    

DOI:10.1002/eji.1830211209

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractThe antigen processing‐defective mutant cell line RMA‐S expresses at the cell surface major histocompatibility complex (MHC) class I molecules devoid of peptide that can be efficiently loaded with exogenous immunogenic peptides. We now report that viral peptide‐loaded RMA‐S cells, unlike parental RMA cells, can induce primary cytotoxic T lymphocyte (CTL) responsesin vitro, in a T helper cell‐independent fashion. This was shown for an H‐2Kb‐binding peptide of Sendai virus nucleoprotein and an H‐2Db‐binding peptide of adenovirus type 5 E1A protein with responding spleen cells of C57BL/6 mice, the strain of origin of RMA and RMA‐S cells. Primary Sendai peptide‐induced CTL lyse both peptide‐loaded and virus‐infected cells. Pre‐culture of RMA‐S cells at low temperature (22°–26°C), which increases the amount of empty MHC class I molecules at the cell surface, decreases the peptide concentrations required for the induction of primary CTL responses. Primary peptide‐specific CTL responses induced by peptide‐loaded RMA‐S cells are CD4+cell‐ and MHC class II+cell‐independent. CTL response induction is blocked by the presence of anti‐CD8 monoclonal antibody during culture. Direct peptide binding studies confirm the efficient loading of empty MHC molecules on RMA‐S cells with peptide and show 2.5‐fold more peptide bound per RMA‐S cell compared to RMA cells. An additional factor explaining the difference in primary response induction between RMA and RMA‐S cells is related to the CD8 dependence of these responses. MHC class I molecules occupied with irrelevant peptides (a majority present on RMA, largely absent on RMA‐S) may interfere in the interaction of the CD8 molecule with relevant MHC/peptide complexes. The results delineate a novel strategy of peptide basedin vit

ISSN:0014-2980    

DOI:10.1002/eji.1830211210

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY

摘要:

AbstractCells secreting antibodies against guinea pig myelin and synthetic myelin basic protein (MBP) peptides were evaluated in cerebrospinal fluid (CSF) and blood from patients with multiple sclerosis (MS) and a variety of other neurological diseases (OND). The peptides used, reproducing amino acid sequences 1–20, 70–89, 108–126, or 157–166 of MBP, were selected on the basis of their hydrophilic and encephalitogenic properties. Low numbers of cells secreting IgG antibodies against myelin or each of the MBP peptides (about 1 per 50000) were detected in peripheral blood, with no difference between MS and OND. In CSF, cells secreting IgG antibodies to MBP 70–89 were more frequently (p= 0.007) detected in patients with MS (1/380 IgG‐secreting cells on average) than in patients with OND (1/2083 IgG‐secreting cells on average). The frequencies of cells secreting antibodies against myelin or the three other MBP peptides were similar in MS and OND. Thus, evaluation of B cell immunity at the cellular level indicates that MBP 70–89 is an immunodominant B cell epitope in MS. It is not clear whether this intrathecal anti‐MBP 70–89 IgG antibody response has any pathogenetic relevance in MS or is the result

ISSN:0014-2980    

DOI:10.1002/eji.1830211211

出版商:WILEY‐VCH Verlag GmbH    

年代:1991

数据来源: WILEY