| First Author | Keppler SJ | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 7 | Pages | e40865 |
| PubMed ID | 22815848 | Mgi Jnum | J:269813 |
| Mgi Id | MGI:6227427 | Doi | 10.1371/journal.pone.0040865 |
| Citation | Keppler SJ, et al. (2012) 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. PLoS One 7(7):e40865 |
| abstractText | 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. |
