title: 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.
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 dependence of CD8 T cells.
authors: Department of Immunology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany.
authors: Selina Jessica
authors: SJ
authors: Keppler
authors: Kerstin
authors: K
authors: Rosenits
authors: Tamara
authors: T
authors: Koegl
authors: Smiljka
authors: S
authors: Vucikuja
authors: Peter
authors: P
authors: Aichele
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D007109:Immunity / Q000276:immunology*; D007239:Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007370:Interferon Type I / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D020825:T-Box Domain Proteins / Q000378:metabolism; D018116:Vesiculovirus / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: C491198:Eomes protein, mouse; D007370:Interferon Type I; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D018664:Interleukin-12