signal 3 cytokines as modulators of primary immune responses during infections the interplay of type i ifn and il-12 in cd8 t cell responses3细胞因子信号调节器的主要免疫反应在感染期间相互作用的i型干扰素和白介素cd8 t细胞反应.pdfVIP

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 1,2. 1,2. 1,2 1 1 Selina Jessica Keppler , Kerstin Rosenits , Tamara Koegl , Smiljka Vucikuja , Peter Aichele * 1 Department of Immunology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany, 2 Faculty of Biology, University of Freiburg, Freiburg, Germany Abstract 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 de