Signal 3 cytokines as modulators of primary immune responses during infections: the interplay of type I IFN and IL-12 in CD8 T cell responses.
Signal 3 cytokines, such as IL-12 or type I IFN, support expansion and differentiation of CD8 T cells in vivo. If and how these two signal 3 cytokines compensate each other in T cell activation during different infections is so far unknown. Using CD8 T cells lacking receptors for IL-12, type I IFN o...
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| Autores principales: | , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2012
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/7d9cdbace882473bbd0211e883de541b |
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| Sumario: | Signal 3 cytokines, such as IL-12 or type I IFN, support expansion and differentiation of CD8 T cells in vivo. If and how these two signal 3 cytokines compensate each other in T cell activation during different infections is so far unknown. Using CD8 T cells lacking receptors for IL-12, type I IFN or both, we show that the expansion of CD8 T cells depends on type I IFN (LCMV infection), type I IFN and IL-12 (Listeria and vesicular stomatitis virus infection) or is largely independent of the two cytokines (vaccinia virus infection). Furthermore, we show that CD8 T cells lacking IL-12 and type I IFN signals are impaired in cytokine production and cytolytic activity in the context of VSV and Listeria infection. These effector CD8 T cells fail to express KLRG1, thereby exhibiting a memory-like phenotype which correlated with lower expression of the transcription factor T-bet and higher expression of Eomes. This indicates that the variable interplay of both signal 3 cytokines is mandatory for cell fate decision of CD8 T cells in the context of different infections. Furthermore our results demonstrate that the pathogen-induced overall inflammatory milieu and not the antigen load and/or the quality of antigen presentation critically determine the signal 3 dependence of CD8 T cells. |
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