2001年5月
Functional uncoupling of T-cell receptor engagement and Lck activation in anergic human thymic CD4(+) T cells
JOURNAL OF BIOLOGICAL CHEMISTRY
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- 巻
- 276
- 号
- 20
- 開始ページ
- 17455
- 終了ページ
- 17460
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- 出版者・発行元
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Human thymic CD1a(-)CD4(+) T cells in the final stage of thymic maturation are susceptible to anergy induced by a superantigen, toxic shock syndrome toxin-1 (TSST-1). Thymic CD4(+) T-cell blasts, established by stimulating human thymic CD1a(-)CD4(+) T cells with TSST-1 in vitro, produce a low level of interleukin-2 after restimulation with TSST-1, whereas TSST-1-induced adult peripheral blood (APB) CD4(+) T-cell blasts produce high levels of interleukin-2. The extent of tyrosine phosphorylation of the T-cell receptor zeta chain induced after restimulation with TSST-1 was 2-4-fold higher in APE CD4(+) T-cell blasts than in thymic CD4(+) T-cell blasts. The tyrosine kinase activity of Lck was low in both thymic and APE CD4(+) T-cell blasts before restimulation with TSST-1, After restimulation, the Lck kinase activity increased in APE CD4(+) T-cell blasts but not in thymic CD4(+) T-cell blasts. Surprisingly, Lck was highly tyrosine-phosphorylated in both thymic and APE CD4(+) T-cell blasts before restimulation with TSST-1, After restimulation, it was markedly dephosphorylated in APE CD4(+) T-cell blasts but not in thymic CD4(+) T-cell blasts. Lck fi om APE CD4(+) T-cell blasts bound the peptide containing the phosphotyrosine at the negative regulatory site of Lck-505 indicating that the site of dephosphorylation in TSST-1-activated T-cell blasts is Tyr-505, Confocal microscopy demonstrated that colocalization of Lck and CD45 was induced after restimulation with TSST-1 in APE CD4(+) T-cell blasts but not in thymic CD4(+) T-cell blasts. Further, remarkable accumulation of Lck in the membrane raft was observed in restimulated APE CD4(+) T-cell blasts but not in thymic CD4(+) T-cell blasts. These data indicate that interaction between Lck and CD45 is suppressed physically in thymic CD4(+) T-cell blasts and plays a critical role in sustaining an anergic state.
- リンク情報
- ID情報
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- ISSN : 0021-9258
- Web of Science ID : WOS:000168730400115