RT Journal Article
T1 p21CIP1/WAF1 Controls Proliferation of Activated/Memory T Cells and Affects Homeostasis and Memory T Cell Responses
A1 Fernández Arias, Cristina
A1 Ballesteros Tato, Andre
A1 García, María Isabel
A1 Martın Caballero, Juan
A1 Flores Landeira, Juana María
A1 Martınez Alonso, Carlos
A1 Balomenos, Dimitrios
AB 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.
PB American Association of Immunologists
YR 2007
FD 2007-02-15
LK https://hdl.handle.net/20.500.14352/96975
UL https://hdl.handle.net/20.500.14352/96975
LA eng
NO Arias CF, Ballesteros-Tato A, García MI, Martín-Caballero J, Flores JM, Martínez-A C, Balomenos D. p21CIP1/WAF1 controls proliferation of activated/memory T cells and affects homeostasis and memory T cell responses. J Immunol. 2007 Feb 15;178(4):2296-306. doi: 10.4049/jimmunol.178.4.2296
DS Docta Complutense
RD 7 abr 2025