Modulation of STAT1 protein levels: a mechanism shaping CD8 T-cell responses in vivo.
Blood
; 107(3): 987-93, 2006 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-16210337
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Transdução de Sinais
/
Interferon Tipo I
/
Regulação da Expressão Gênica
/
Linfócitos T CD8-Positivos
/
Fator de Transcrição STAT1
Limite:
Animals
Idioma:
En
Revista:
Blood
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos