P27kip1 regulates the cell cycle arrest and survival of activated T lymphocytes in response to interleukin-2 withdrawal.
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 p27kip1. Comparison with resting T-cell populations revealed that the highest expression of p27kip1 occurs in activated T cells undergoing cell cycle arrest following IL-2 withdrawal. T cells deficient in p27kip1 expression showed an impaired ability to undergo cell cycle arrest in response to IL-2 deprivation. Moreover, T cells deficient in p27kip1 showed significantly more apoptosis after IL-2 withdrawal. Collectively, this study demonstrates that p27kip1 regulates both the cell cycle arrest and the apoptosis of antigen-specific T lymphocytes.
Huleatt
James W
JW
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA. James.Huleatt@Yale.edu
Cresswell
James
J
Bottomly
Kim
K
Crispe
I Nicholas
IN
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002453:Cell Cycle / Q000276:immunology / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D007376:Interleukin-2 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D007376:Interleukin-2; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27