Thymus最新文献

{"title":"Thymic repertoire selection by superantigens: presentation by human and mouse MHC molecules.","authors":"E Simpson,&nbsp;K Takacs,&nbsp;D M Altmann","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The initial report of T cell receptor (TCR) V beta-specific thymic selection in mice showed association with expression of H-2E molecules and affected V beta 17a T cells which were present in CD4+8+ double positive thymocytes but deleted from the CD4+ and CD8+ single positive populations. Similar deletions were subsequently reported for V beta 8.1+ and V beta 6+ T cells in Mls-1a mouse strains and for V beta 3+ T cells in Mls-2a/3a strains. The 'Mls antigens' are most effectively presented by H-2E molecules but certain alleles of H-2A molecules can also present these endogenous superantigens. Expression of Mls antigens can cause both V beta-specific thymic deletion and stimulation of peripheral T cells from Mls-negative strains. Another category of 'Mls-like' antigens cause only V beta-specific thymic deletion in H-2E+ strains, affecting V beta 5+ and V beta 11+ T cells. The non-MHC ligands responsible for each of these effects are superantigens analogous to the exogenous bacterial superantigens, which also show TCR V beta-specific stimulatory effects when presented by MHC class II positive antigen-presenting cells. The genes encoding endogenous superantigens in mice were shown to co-segregate with mouse mammary tumour virus integrations (Mtv) and to be the Mtv-LTR orf genes. In vitro translation of Mtv-LTR orf genes identified their products as type II integral membrane glycoproteins with the polymorphic C terminus outside the cell. These polymorphisms correlate with specificity for the different TCR V beta chains. Virtually all TCR V beta-specific negative selection in the mouse thymus can be accounted for by the expression of Mtv or MMTV (the infectious counterparts of Mtv proviral integrants) LTR-orf proteins, presented with H-2E or certain H-2A alleles. It is unlikely that TCR V beta-specific positive selection is due to endogenous superantigens since it does not segregate with Mtv genomes. In humans, HLA-DR molecules appear to be homologous with H-2E in mice whereas HLA-DQ are the homologues of H-2A. H-2E negative mice transgenic for HLA-DR alpha chain express a mouse/human heterodimeric molecule which presents Mtv superantigens causing TCR V beta-specific deletion. Such trans-species class II molecules are also effective in TCR V beta-specific positive selection of V beta 2+, V beta 6+ and V beta 10+ T cells. Taken together, these results show that human MHC class II molecules can interact with the murine T cell repertoire.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"23 1","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18861510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of bovine growth hormone administration on the pattern of thymic involution in mice.","authors":"Y Bar-Dayan,&nbsp;M Small","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Age-related decline of the thymus in mice was reversed by repeated injections of bovine growth hormone. After hormone administration that was begun at 5, 8, or 11.5 months of age, the cortical volume fraction (Vc), cortical/medullary ratio (C/M) and thymocyte numbers found were in the range obtained with younger mice. Growth hormone injection reduced the slope of the curves for Vc and C/M as a function of age, indicating a slowing down of the involution process.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"23 2","pages":"95-101"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18726510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro effects of deoxyguanosine (dGuo) on thymic stromal cells. A discussion.","authors":"A Martín-Fontecha,&nbsp;H J Schuurman,&nbsp;A Zapata","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Different in vitro approaches have been used to enrich thymic epithelial cells for the analysis of their role in inducing tolerance. One widely used approach consists of the organ culture of mouse fetal thymic lobes (FTOCs) in the presence of 2'-deoxyguanosine (dGuo), that is thought to selectively eliminate both thymocytes and interdigitating cells/dendritic cells (IDCs/DCs) from the thymic cultured tissue. The dGuo-induced effects on rat thymic stromal cells appear to differ from those described in mouse. In this paper we present evidence supporting the presence of rat DCs in both thymic cultured fragments and thymic stromal cell primary cultures after dGuo treatment. Possible explanations for these contradictory results are discussed.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"22 3","pages":"167-76"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18937168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbial parasites versus developing T cells: an evolutionary 'arms race' with implications for the timing of thymic involution and HIV pathogenesis.","authors":"P W Turke","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The thymus attempts to ensure that T cells which emerge from it are able to discriminate self from nonself. As such, it is a potential 'backdoor' through which microbial parasites can enter, manipulate the host into perceiving them as 'self', and thereby avoid immune surveillance. It is proposed that the host has evolved to overcome this parasitic strategy by rapidly producing large numbers of long-lived T cells very early in life (closing the backdoor), before the developing individual has significant contact with infectious organisms, and while still under the protection of its mother's intact immune system. Hence the capacity of the thymus to function efficiently early in the lifespan would have been strongly favored by natural selection. It is well established in evolutionary biology that strong selection favoring enhanced early function easily accommodates, through pleiotropy, the accumulation of later occurring negative effects, and it is through this process that thymic involution and subsequent immune system senescence may have evolved. Once a large pool of competent T cells has been produced, even those microbes capable of contaminating the thymus usually can be eliminated, or at least contained. However, microbes that both destroy peripheral T cells (particularly peripheral T cells that are activated against them), and contaminate the thymus (leading to deletion of potential replacements of the destroyed peripheral cells), may be able to eventually overcome the immune system, thus producing disease after a long period of apparent latency. Human immunodeficiency virus, which is initially well controlled by the immune system, may become unleashed via this process.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"24 1","pages":"29-40"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19607754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental control of T-cell receptor internalization.","authors":"F Luton,&nbsp;M Buferne,&nbsp;A M Schmitt-Verhulst,&nbsp;C Boyer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Since TCR/CD3 modulation may be involved in induction of T cell tolerance to self antigens, we compared ligand-induced TCR/CD3 internalization by a CTL clone and by immature thymocytes and mature T cells from mice bearing the same TCR alpha beta as transgene. The ligand used is a monoclonal antibody (mAb) specific for the receptor expressed by the clone and transgenic mice (anti-Ti mAb). CD8+ splenocytes triggered by anti-Ti mAb internalize the ligand-TCR/CD3 complex at a low rate, through a mechanism inhibited by the protein tyrosine kinase (PTK) inhibitor genistein and by staurosporine, a potent but non selective protein kinase C (PKC) inhibitor. This pattern of inhibition was similar to that observed in the CTL clone. Anti-Ti mAb induced TCR/CD3 internalization in CD4+CD8+ thymocytes at a high rate, through a mechanism which was insensitive to either genistein or staurosporine. In the CTL clone, genistein was shown to inhibit TCR/CD3 surface redistribution preceeding internalization. To characterize the PTK possibly involved in this step, we analyzed TCR/CD3 associated kinases in mature T splenocytes and thymocytes. Kinase activities present in anti-Ti mAb immunoprecipitates phosphorylated the CD3 components gamma, delta, epsilon, and zeta in both cell types although the intensity was stronger in splenic than in thymocyte extracts, whereas the phosphorylation of 70, 14 and 12kD substrates was more pronounced in thymocytes than in splenocytes. Comparable amounts of CD3 components were coprecipitated with and phosphorylated by p56lck and p59fyn respectively, in both cell types.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"23 1","pages":"15-25"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18861511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thymic stromal cells eliminate T cells stimulated with antigen plus stromal Ia molecules through their cross-talk involving the production of interferon-gamma and nitric oxide.","authors":"X G Tai,&nbsp;Y Saitoh,&nbsp;T Satoh,&nbsp;N Yamamoto,&nbsp;Y Kita,&nbsp;H Takenaka,&nbsp;W G Yu,&nbsp;J P Zou,&nbsp;T Hamaoka,&nbsp;H Fujiwara","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We previously established a thymic stromal cell clone capable of inducing differentiation of immature thymocytes and described a clonal elimination model in which T cell clones are killed on the monolayer of this stromal clone by stimulation of their T cell receptors (TCR) with antigen plus stromal Ia molecules. This study investigated molecular mechanisms underlying this phenomenon. Antigenic stimulation on thymic stromal cells produced large amounts of interferon-gamma (IFN-gamma) and small amounts of tumor necrosis factor-alpha (TNF-alpha). Addition of anti-IFN-gamma monoclonal antibody (mAb) to these cultures largely prevented death of TCR-stimulated T cells. T cell death was also induced when cultures were treated with recombinant IFN-gamma (rIFN-gamma) or rTNF-alpha instead of the relevant antigen, showing that these lymphokines are involved in the process of T cell death. It was further demonstrated that these lymphokines, especially IFN-gamma, induced the expression of mRNA for the inducible type of nitric oxide (NO) synthase in thymic stromal cells and that enhanced levels of NO were produced by stromal cells cultures with T cells plus antigen or stimulated with rIFN-gamma or rTNF-alpha. NO was found to be critically responsible for inducing T cell death on the stromal cell monolayer following stimulation of T cells with antigen or of stromal cells with rIFN-gamma or rTNF-alpha, because T cells death was completely prevented by addition of NG-monomethyl-L-arginine (L-NMMA), which is capable of inhibiting NO production. These results indicate that elimination of TCR-stimulated T cells on thymic stromal monolayers with the capacity to support thymocyte differentiation is induced by the cross-talk between IFN-gamma/TNF-alpha-producing T cells and stromal cells capable of producing NO in response to these lymphokines.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"24 1","pages":"41-56"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19607635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin E supplementation at various levels alters cytokine production by thymocytes during retrovirus infection causing murine AIDS.","authors":"Y Wang,&nbsp;R R Watson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Female C57BL/6 mice were infected with LP-BM5 retrovirus, causing murine AIDS which is functionally similar to human AIDS. Retrovirus infection targets the thymus producing altered T-cell differentiation via the dysregulation of thymocyte cytokine production. Therefore the effects of dietary vitamin E at various levels were determined on cytokine production by ConA-stimulated thymocytes from uninfected (normal) and retrovirus-infected mice. Dietary supplementation, with a 15-, 150- and 450-fold increase of vitamin E in the diet modulated interleukin-2 (IL) production in both uninfected mice and retrovirus-infected mice. The 150- and 450-fold vitamin E supplementation significantly reduced IL-4 secretion by thymocytes from the uninfected, normal mice. Supplementation at all levels also significantly reduced IL-4 production by thymocytes, which was elevated by the retrovirus infection. Vitamin E significantly reduced IL-6 and interferon-gamma production increased during the progression to murine AIDS. The effects of dietary vitamin E on conA-induced proliferation of thymocytes were consistent with the finding on changes of IL-2 secretion. No effect of dietary vitamin E on thymus weight was observed in both uninfected and retrovirus-infected mice. These data indicate that dietary vitamin E supplementation at extremely high levels can modulate cytokine production by thymocytes. This could affect T-cell differentiation, especially during murine AIDS when cytokine production was partially normalized by vitamin E supplementation.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"22 3","pages":"153-65"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18937166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thymus involvement in murine acquired immunodeficiency (MAIDS).","authors":"S Colombi,&nbsp;M Deprez,&nbsp;L De Leval,&nbsp;C Humblet,&nbsp;R Greimers,&nbsp;M P Defresne,&nbsp;J Boniver,&nbsp;M Moutschen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Due to self-renewal of the peripheral pool of T-cells, adult thymectomy has normally little influence on immunocompetence. However, thymus might play a more important role in the setting of viral-induced cytopathic effects on T-cells in the periphery. Therefore, thymus weight, cell numbers, and subset distribution were sequentially analysed after infection with RadLV-Rs, a viral mixture known to induce murine retrovirus induced immunodeficiency (MAIDS). Infection induced thymic atrophy (concerning organ weight as well as total cell number) which culminated seven weeks after inoculation. The atrophic process mostly reflected the depletion of double positive CD4+ CD8+ cells since their proportion sharply decreased around week 6. Single positive T-cells were less affected by the process. The proportion of B-cells progressively increased. Surprisingly, there was a strong correlation between the extent of atrophy and the frequency of B-cells in the thymus. Finally, an abnormal CD4+ T-cell subset lacking Thy-1 and previously described in the periphery also appeared in the thymus and its frequency was strongly correlated with the expansion of B-cells in this organ.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"23 1","pages":"27-37"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18539666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD8 requirements for negative selection events are directly related to the TCR-antigen interaction.","authors":"S J Curnow,&nbsp;A Guimezanes,&nbsp;A M Schmitt-Verhulst","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Positive selection of class I-restricted T cells has been suggested to always require the surface expression of CD8 molecules on CD4+8+ thymocytes, whilst negative selection was found to be differentially dependent, relating to the antigen being engaged by the T cell receptor (TCR). We have studied the CD8-dependency of positive and negative selection using two TCR-transgenic (Tg) mice models, which both react against the same allo-antigen, H-2kb, back crossed with mice which are deficient for the expression of CD8. Whilst CD8 expression was always required for positive selection of cells expressing high levels of the Tg-TCR, events of negative selection were differentially dependent upon CD8, reflecting the CD8-dependency of the original CTL clones. For one TCR-Tg model (derived from a CD8-dependent CTL clone), deletion of CD4+8+ thymocytes was partially dependent upon the expression of CD8, though there was still selection against Tg-TCR positive CD4+ cells, which normally exit to the periphery expressing low levels of Tg-TCR. For the other model (derived from a CD8-independent CTL clone) negative selection was unaffected by the absence of CD8. For both models the CD4-8- Tg-TCR positive population was unaffected by the absence of CD8, including, for the CD8-independent model, reduced expression of the Tg-TCR/CD3 complex. These results suggest that CD8 expression may be a prerequisite for positive selection, whilst negative selection events can occur in the absence of CD8, depending directly upon the TCR-antigen interaction.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"22 4","pages":"255-65"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18984215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution of molecules mediating thymocyte-stroma-interactions in human thymus, thymitis and thymic epithelial tumors.","authors":"A Marx,&nbsp;D Schömig,&nbsp;A Schultz,&nbsp;S Gattenlöhner,&nbsp;A Jung,&nbsp;T Kirchner,&nbsp;A Melms,&nbsp;H K Müller-Hermelink","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Two findings in thymic epithelial tumors are correlated with the occurrence of myasthenia gravis(MG): (1) the expression of an acetylcholine receptor (AChR)-like-epitope in the neoplastic epithelium, and (2) the preservation of thymus-like features in the neoplasms, indicated by the presence of immature thymocytes. On this background it has been proposed that paraneoplastic MG may start with an intratumorous abnormal T cell selection due to aberrantly expressed AChR-epitopes (self-peptides). As appropriate thymocyte-stroma-interactions are prerequisites for thymocyte development in the thymus (and probably in MG-associated thymic tumors, too), we analyzed the expression of CD28/B7(BB1), CD2/:LFA3, LFA-1/ICAM-1 and VLA-4/VCAM-1 in human thymus and thymomas by immunohistochemistry. In normal thymuses and thymitis the stromal molecules were expressed at higher levels in the medulla than in the cortex. This was particularly true for B7(BB1) that was undetectable by immunoperoxidase techniques in the cortex. In contrast, cortical-type thymic epithelial tumors (cortical thymoma and well differentiated thymic carcinoma), known to exhibit the highest association with myasthenia, expressed the stromal molecules at almost medullary levels. The findings may be a clue to a functional difference between neoplastic and normal cortical epithelial cells: while we find the former to have the capacity to present soluble antigen to antigen-specific CD4+ T cells in vitro, normal cortical epithelium failed to do so. This altered microenvironment in thymomas might contribute to the autoimmunization by stimulating mature recirculating AChR-specific T cells.</p>","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"23 2","pages":"83-93"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18726509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}