Study of T lymphocytes which develop in the extrathymic tissues.

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It has been accepted that T cells recognize forein antigens in association with MHC. This T cell nature is postulated to be selectively generated during the intrathymic differentiation. despite many trials, the selection mechanism is still remained unclear. In athymic nude mice, the presence of Thy-1<@D1+@>D1 cells has been reported. To clarify whether the thymus specific function is really required for the MHC restricted T cell generation, we adressed this study to identify the differentiation stages and the characteristics of The-1<@D1+@>D1 lymphocytes in the nude mice in comparison with normal intrathymic differentiation. The study of phenotype expression in the nude lymphocytes demonstrated that the Thy-1<@D1+@>D1cells are CD4<@D1-@>D1 and CD8<@D1-@>D1 in 6-week old mice. However, in aged mice, the proportion of Thy-1<@D1+@>D1cells increased and CD4<@D1+@>D1 or CD8<@D1+@>D1cells appeared. These CD4<@D1+@>D1 and CD8<@D1+@>Dcells also expressed CD3, implying they express T cell antig … More en receptor(TCR). In fact, sourthern blot analysis using TCR gene probe showed that B-chain genes are rearranged in the phenotypically mature nude T cells. In addition, these nude T cells showed MLR and Con A reactive ability. These observations indicate that functionally mature T cells can delevop out of the thymus. We demonstrated a direct evidence of T cell differentiation pathway from CD4<@D1-@>D1CD8<@D1-@>D1 go CD4<@D1+@>D1 or CD8<@D1+@>D1 cells through CD4<@D1+@>D1CD8<@D1+@>D1 cells in the thymus. In nude mice, CD4<@D1+@>D1CD8<@D1+@>D1 cells were not detectable but when CD4<@D1+@>D1CD8<@D1+@>D1 thymocytes were transfered into the nude mice, they develop in CD4<@D1+@>D1 and CD8<@D1+@>D1 cells. These observations suggest that in the extrathymic tissued, immature T cells may develop into mature T cells without CD4<@D1+@>D1CD8<@D1+@>D1 differentiation stage. CD8<@D1+@>D1CD8<@D1+@>D1 thymocytes are candidates of targets for negative selection. If that is a case, the nude mouse may be a good model to study tolerance mechanism. Less