| First Author | Duré M | Year | 2009 |
| Journal | Mol Immunol | Volume | 46 |
| Issue | 5 | Pages | 999-1006 |
| PubMed ID | 18990450 | Mgi Jnum | J:145024 |
| Mgi Id | MGI:3833183 | Doi | 10.1016/j.molimm.2008.09.029 |
| Citation | Dure M, et al. (2009) IL-2 signaling prevents T cell anergy by inhibiting the expression of anergy-inducing genes. Mol Immunol 46(5):999-1006 |
| abstractText | T cell responses are determined by the environment in which antigen is encountered. In the absence of proper costimulation, anergizing stimuli induce the activation of a specific program of gene expression. Proteins encoded by these genes impose a state of functional unresponsiveness in anergic T cells through the activation of different mechanisms that include dampening of the T cell receptor signaling and direct inhibition of cytokine expression. Anergy can be reversed by stimulating T cells in the presence of interleukin (IL-)2. Signaling through the IL-2 receptor has been shown to activate mTOR, which plays an important role in the integration of signals that determine the fate of T cells. The mechanisms underlying the IL-2-dependent regulation of T cell tolerance are still not fully elucidated. In this study we show that IL-2 receptor signaling mediated through JAK3 and mTOR inhibits the expression of anergy-inducing genes independently of any effect on cell cycle progression. Interestingly, we also show that this effect is likely due to changes on the levels of AP-1 activation induced by IL-2 receptor signaling in T cells. Our data identifies a mechanism that can explain how IL-2 may prevent or reverse the establishment of anergy in T cells and, therefore, helps to understand how the cytokine environment can be determinant to shape the outcome of T cell responses |
