| Co-Investigator(Kenkyū-buntansha) |
ITO Mamoru Central Institute for Experimental Animals, Chief of Immunology, 免疫研究所, 室長 (00176364)
SATO Takehito Tokai Univ.Sch.Medicine, Instractor, 医学部, 助手 (50235363)
ANDO Kiyoshi Tokai Univ.Sch.Medicine, Assistant Professor, 医学部, 講師 (70176014)
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| Research Abstract |
In the intrathymic development, only DP cells which are rescued from the cell death by TCR mediated selecting development into SP cells. At the same time, it is strongly suggested that apoptosis of DP cells is inhibited when TCR mediated signaling suppresses further rearrangement of TCR-alpha gene. In this study, we investigated the molecular mechanism of cell survival /proliferating suppression on DP cells receiving positive selection, and obtained the following results. 1) CD45 is involved in proloferating suppression of DP cells. 2) DP cells easily die when DP cells receive TCR mediated signaling at the proliferating stage. 3) JNK, one of MAPK family, functions for the positive selection by blocking the cell death of DP cells, which was provident when DP cells is integrated with dominant negative gene of Seki, a JNK kinase, showed apoptosis. 4) As a novel cis- element with a stage specificity, the upstream region of Jalpha49 segment was shown to regulated the gene rearrangement and germ line transcription of Jct49-45. This indicates that TCR-alpha gene rearrangement requires a stage specific cis-element as well as alpha enhancer.
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