Mice deficient for N-ras: impaired antiviral immune response and T-cell function.
Cancer Res
; 63(7): 1615-22, 2003 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-12670913
ABSTRACT
Ras proteins have a key role in the regulation of several cellular functions, and are involved in a significant percentage of human tumors. However, the specific functions of the different Ras isoforms are poorly understood. In this work, we show for the first time a specific role for N-ras in T-cell function and development. Mice defective for N-ras have low numbers of CD8 single positive thymocytes and decreased thymocyte proliferation in vitro. In Ras signaling and activation assays, KO-N-ras thymocytes showed a defective response to T-cell activation. In turn, these deficiencies resulted in a significant reduction in the production of interleukin 2 on thymocyte activation. We have also detected in vivo the functional consequences of N-ras deficiency. KO-N-ras mice showed an increased sensitivity to influenza infection, especially when low doses of virus were used. Finally, we have detected an abnormal activation pattern of downstream Ras molecules in T-cell receptor-activated KO-N-ras thymocytes that is consistent with the defective T-cell function found in these animals. All of the results derived from this work constitute a significant contribution to the knowledge of N-ras-specific functions.
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Base de dados:
MEDLINE
Assunto principal:
Vírus da Influenza A
/
Genes ras
/
Infecções por Orthomyxoviridae
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Proteínas ras
/
Linfócitos T CD8-Positivos
Limite:
Animals
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article