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Molecular mechanism of apoptosis in the selection of T cells in the human thymus

Research Project

Project/Area Number 11671334
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionNAGOYA CITY UNIVERSITY

Principal Investigator

SAITO Yushi  Nagoya City University, Medical School, Research Associate, 医学部, 助手 (80281260)

Co-Investigator(Kenkyū-buntansha) FUJII Yoshitaka  Nagoya City University, Medical School, Professor, 医学部, 教授 (40156831)
KAJI Masahiro  Nagoya City University, Medical School, Research Associate, 医学部, 助手 (30326144)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsProtein kinase C / ionomycin / positive selection / CD4 down-regulation / bcl-2 / Protein Kinase C / caspase / bcl-x / bax / bak / bim
Research Abstract

Positive selection of immature thymocytes is a developmental process in which TCR ligation with low avidity induces generation of mature T cells. In mouse thymocytes, CD4+8+ double-positive (DP) cells which were treated with a proper combination of calcium ionophore and phorbol 12-myristate 13-acetate (PMA) have been reported to differentiate into CD4 single positive cells. However in human thymocytes the effects of PMA and ionomycin have remained unclear. Here we report that DP cells that were treated with PMA and ionomycin up-regulated bcl-2 and down-regulated CD1 expression. However, CD3 expression remained low. This treatment induced prolonged CD4 down-regulation in DP cells which was an effect also seen in mature peripheral blood T cells. PMA/ionomycin-treated DP cells showed high cell proliferation and resistance to apoptosis. These results indicate that PKC activation and calcium elevation may be part of the biochemical signals that induce positive selection of human DP cells and may be a useful model to study the signals involved in the selection of human thymocytes.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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