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- Title
p27<sup>kip1</sup> functions as an anergy factor inhibiting interleukin 2 transcription and clonal expansion of alloreactive human and mouse helper T lymphocytes.
- Authors
Boussiotis, Vassiliki A.; Freeman, Gordon J.; Taylor, Patricia A.; Berezovskaya, Alla; Grass, Isabelle; Blazar, Bruce R.; Nadler, Lee M.
- Abstract
Although recent in vitro studies have begun to decipher the molecular events that characterize the anergic state, their in viva biologic relevance and potential clinical importance remain unclear. Here, using anergic human T-cell clones and tolerant alloreactive mouse T cells that do not induce graft-versus-host disease, we show that p27[sup kip1] cyclin-dependent kinase inhibitor is an essential regulator responsible for the blockade of clonal expansion of anergic T cells in vitro and in viva. Moreover, in anergic cells, p27[sup kip1] associates with the c-Jun co-activator JAB1, resulting in defective transactivation of AP-1 and interleukin 2 transcription. Therefore, pharmacological agents that upregulate the expression of or prevent the degradation of p27[sup kip1] during antigen recognition should be part of new therapeutic strategies to induce antigen-specific T-cell unresponsiveness.
- Publication
Nature Medicine, 2000, Vol 6, Issue 3, p290
- ISSN
1078-8956
- Publication type
Academic Journal
- DOI
10.1038/73144