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P27 kip1 regulates the cell cycle arrest and survival of activated T lymphocytes in response to interleukin‐2 withdrawal
Author(s) -
Huleatt James W.,
Cresswell James,
Bottomly Kim,
Crispe I. Nicholas
Publication year - 2003
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2003.01605.x
Subject(s) - cell cycle , apoptosis , cell cycle checkpoint , t cell , biology , microbiology and biotechnology , interleukin 2 , immune system , downregulation and upregulation , cell , t lymphocyte , interleukin , immunology , cytokine , biochemistry , gene
Summary The majority of activated T lymphocytes undergo cell death at the end of a primary immune response, while a minority survive as memory cells. The mechanisms that control the decision between these two fates are unknown. In the present study we examined the response of activated T cells to interleukin‐2 (IL‐2) withdrawal. Within hours, the percentage of T lymphocytes in cell cycle showed a steady decrease, while the percentage arrested in G1 increased proportionally. Deprivation of IL‐2 resulted in upregulation of the cell cycle inhibitor p27 kip1 . Comparison with resting T‐cell populations revealed that the highest expression of p27 kip1 occurs in activated T cells undergoing cell cycle arrest following IL‐2 withdrawal. T cells deficient in p27 kip1 expression showed an impaired ability to undergo cell cycle arrest in response to IL‐2 deprivation. Moreover, T cells deficient in p27 kip1 showed significantly more apoptosis after IL‐2 withdrawal. Collectively, this study demonstrates that p27 kip1 regulates both the cell cycle arrest and the apoptosis of antigen‐specific T lymphocytes.