1988 Fiscal Year Final Research Report Summary

Study of T lymphocytes which develop in the extrathymic tissues.

Research Project

Project/Area Number	61480139
Research Category	Grant-in-Aid for General Scientific Research (B)
Allocation Type	Single-year Grants
Research Field	Experimental pathology
Research Institution	Tokai University School of Medicine
Principal Investigator	HABU Sonoko Tokai University School of Medicine, Professor, 医学部, 教授 (30051618)
Co-Investigator(Kenkyū-buntansha)	MORIUCHI Tetsuya Tokai University School of Medicine, Assistant Professor, 医学部, 講師 (20174394) KATSUKI Motoya Tokai University School of Medicine, Professor, 医学部, 教授 (20051732) TAMAOKI Norikazu Tokai University School of Medicine, Professor (50055860)
Project Period (FY)	1986 – 1988
Keywords	Nude mouse / Thymus-independent T cells / Immature T cells / Cell surface molecules / T細胞抗原レセプター
Research Abstract	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