p21CIP1/WAF1 controls proliferation of activated/memory T cells and affects homeostasis and memory T cell responses

Academic Article

Abstract

  • Development of autoantibodies and lupus-like autoimmunity by 129/Sv x C57BL/6 p21-/- mice has established that cell cycle deregulation is one the defective pathways leading to break of tolerance. Memory T cell accumulation is thought to be related to tolerance loss in murine lupus models. We studied T cell memory responses in C57BL/6 p21-/- mice that develop lupus-like disease manifestations. p21 did not affect primary proliferation of naive T cells, and was required for cycling control, but not for apoptosis of activated/memory T cells. When we induced apoptosis by secondary TCR challenge, surviving memory T cells depended on p21 for proliferation control. Under conditions of secondary T cell stimulation that did not cause apoptosis, p21 was also needed for regulation of activated/memory T cell expansion. The requirement for p21 in the control of T cell proliferation of activated/memory T cells suggests that in addition to apoptosis, cycling regulation by p21 constitutes a new pathway for T cell homeostasis. Concurring with this view, we found accumulation in p21-/- mice of memory CD4+ T cells that showed increased proliferative potential after TCR stimulation. Furthermore, OVA immunization of p21-/- mice generated hyperresponsive OVA-specific T cells. Overall, the data show that p21 controls the proliferation of only activated/memory T cells, and suggest that p21 forms part of the memory T cell homeostasis mechanism, contributing to maintenance of tolerance. Copyright © 2007 by The American Association of Immunologists, Inc.
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    Digital Object Identifier (doi)

    Author List

  • Arias CF; Ballesteros-Tato A; García MI; Martín-Cabalero J; Flores JM; Martínez-A C; Balomenos D
  • Start Page

  • 2296
  • End Page

  • 2306
  • Volume

  • 178
  • Issue

  • 4