| First Author | Cousens LP | Year | 1999 |
| Journal | J Exp Med | Volume | 189 |
| Issue | 8 | Pages | 1315-28 |
| PubMed ID | 10209048 | Mgi Jnum | J:54482 |
| Mgi Id | MGI:1335956 | Doi | 10.1084/jem.189.8.1315 |
| Citation | Cousens LP, et al. (1999) Two roads diverged: interferon alpha/beta- and interleukin 12-mediated pathways in promoting T cell interferon gamma responses during viral infection. J Exp Med 189(8):1315-28 |
| abstractText | Viral infections induce CD8 T cell expansion and interferon (IFN)-gamma production for defense, but the innate cytokines shaping these responses have not been identified. Although interleukin (IL)-12 has the potential to contribute, IL-12-dependent T cell IFN-gamma has not been detected during viral infections. Moreover, certain viruses fail to induce IL-12, and elicit high levels of IFN-alpha/beta to negatively regulate it. The endogenous factors promoting virus-induced T cell IFN-gamma production were defined in studies evaluating CD8 T cell responses during lymphocytic choriomeningitis virus infections of mice. Two divergent supporting pathways were characterized. Under normal conditions of infections, the CD8 T cell IFN-gamma response was dependent on endogenous IFN-alpha/beta effects, but was IL-12 independent. In contrast, in the absence of IFN-alpha/beta functions, an IL-12 response was revealed and substituted an alternative pathway to IFN-gamma. IFN-alpha/beta-mediated effects resulted in enhanced, but the alternative pathway also promoted, resistance to infection. These observations define uniquely important IFN-alpha/beta-controlled pathways shaping T cell responses during viral infections, and demonstrate plasticity of immune responses in accessing divergent innate mechanisms to achieve similar ultimate goals. |
