| First Author | Gil MP | Year | 2006 |
| Journal | Blood | Volume | 107 |
| Issue | 3 | Pages | 987-93 |
| PubMed ID | 16210337 | Mgi Jnum | J:127570 |
| Mgi Id | MGI:3763943 | Doi | 10.1182/blood-2005-07-2834 |
| Citation | Gil MP, et al. (2006) Modulation of STAT1 protein levels: a mechanism shaping CD8 T-cell responses in vivo. Blood 107(3):987-93 |
| abstractText | Type 1 interferons (IFNs) are induced in vivo, administered therapeutically, and potential targets for amelioration of autoimmune diseases. The cytokines mediate profound antiproliferative effects. Signal transducer and activator of transcription 1 (STAT1)-dependent signaling pathways are required for inhibition of proliferation, and viral infections can elicit high levels of type 1 IFNs as well as total STAT1 protein expression. Thus, a mechanism must be in place to help antigen-specific T cells overcome IFN-induced inhibition of proliferation. The studies reported here demonstrate that total CD8 T-cell proliferation in the presence of IFNs, ex vivo in response to cytokines and in vivo during viral infection, is inhibited through a STAT1-dependent mechanism. In contrast, major proportions of antigen-specific CD8, but not CD4, T cells are rendered less sensitive to this inhibition, express lower endogenous levels of total STAT1, and are selectively proliferating in the presence of type 1 IFN, at key times after viral challenge. Taken together, these novel results show that differential STAT1 expression is used by the immune system to modify cytokine-mediated effects on T-cell expansion and have implications for the consequences of therapeutic intervention in cytokine function. |
