| First Author | Arias CF | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 4 | Pages | 2296-306 |
| PubMed ID | 17277135 | Mgi Jnum | J:143984 |
| Mgi Id | MGI:3829558 | Doi | 10.4049/jimmunol.178.4.2296 |
| Citation | Arias CF, et al. (2007) p21CIP1/WAF1 controls proliferation of activated/memory T cells and affects homeostasis and memory T cell responses. J Immunol 178(4):2296-306 |
| abstractText | 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. |
