| First Author | Zhang S | Year | 2000 |
| Journal | J Immunol | Volume | 165 |
| Issue | 11 | Pages | 6270-7 |
| PubMed ID | 11086062 | Mgi Jnum | J:112128 |
| Mgi Id | MGI:3655567 | Doi | 10.4049/jimmunol.165.11.6270 |
| Citation | Zhang S, et al. (2000) Cytokine-stimulated T lymphocyte proliferation is regulated by p27Kip1. J Immunol 165(11):6270-7 |
| abstractText | T lymphocyte growth is regulated by the cyclin-dependent kinase inhibitor p27(Kip1). Mice deficient in p27(Kip1) have increased proliferative responses to multiple cytokines, including IL-2, IL-4, and IL-12, but not to anti-CD3. In the absence of p27(Kip1), T cells proliferate faster than control cells, as evidenced by increased [(3)H]thymidine uptake, increased cell growth and division, and an increased number of cells in S phase. Importantly, this regulation is specific for p27(Kip1) in T cells, because hyperproliferation of T cells from mice deficient in p21(Cip1/Waf1) was not observed. In vivo, there is an expansion of activated/memory CD4(+) cells in p27(Kip1)-deficient mice before and after immunization. Furthermore, Ag-stimulated spleen cells from immunized p27(Kip1)-deficient mice demonstrated increased proliferative responses to IL-2 and increased secretion of IFN-gamma. Although IL-4 stimulated proliferative responses are diminished in Stat6-deficient T cells, activated T cells from mice doubly deficient in both p27(Kip1) and Stat6 recover normal proliferative responses to IL-4. Together, these data firmly support a role for p27(Kip1) as a negative regulator of cytokine-stimulated T cell growth. |
