| First Author | Jatzek A | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 11 | Pages | 5119-28 |
| PubMed ID | 23071285 | Mgi Jnum | J:190697 |
| Mgi Id | MGI:5449481 | Doi | 10.4049/jimmunol.1201482 |
| Citation | Jatzek A, et al. (2012) p27(Kip1) negatively regulates the magnitude and persistence of CD4 T cell memory. J Immunol 189(11):5119-28 |
| abstractText | Much is known about the differentiation of naive T cells into distinct lineages of effector cells, but the molecular mechanisms underlying the generation and maintenance of CD4 T cell memory are poorly characterized. Our studies ascribe a novel role for the cell cycle regulator p27(Kip1) as a prominent negative regulator of the establishment and long-term maintenance of Th1 CD4 T cell memory. We demonstrate that p27(Kip1) might restrict the differentiation and survival of memory precursors by increasing the T-bet/Bcl-6 ratio in effector CD4 T cells. By promoting apoptosis and contraction of effector CD4 T cells by mechanisms that are at least in part T cell intrinsic, p27(Kip1) markedly limits the abundance of memory CD4 T cells. Furthermore, we causally link p27(Kip1)-dependent apoptosis to the decay of CD4 T cell memory, possibly by repressing the expression of gamma-chain receptors and the downstream effector of the Wnt/beta-catenin signaling pathway, Tcf-1. We extend these findings by showing that the antagonistic effects of p27(Kip1) on CD4 T cell memory require its cyclin-dependent kinase-binding domain. Collectively, these findings provide key insights into the mechanisms underlying the governance of peripheral CD4 T cell homeostasis and identify p27(Kip1) as a target to enhance vaccine-induced CD4 T cell memory. |
