title: IL-12 Signals through the TCR To Support CD8 Innate Immune Responses.
abstract: CD8 T cells must integrate antigenic and inflammatory signals to differentiate into efficient effector and memory T cells able to protect us from infections. The mechanisms by which TCR signaling and proinflammatory cytokine receptor signaling cooperate in these processes are poorly defined. In this study, we show that IL-12 and other proinflammatory cytokines transduce signals through the TCR signalosome in a manner that requires Fyn activity and self-peptide-MHC (self-pMHC) interactions. This mechanism is crucial for CD8 innate T cell functions. Loss of Fyn activity or blockade of self-pMHC interactions severely impaired CD8 T cell IFN-γ and NKG2D expression, proliferation, and cytotoxicity upon cytokine-mediated bystander activation. Most importantly, in the absence of self-pMHC interactions, CD8 memory T cells fail to undergo bystander activation upon an unrelated infection. Thus, CD8 T cell bystander activation, although independent of cognate Ag, still requires self-pMHC and TCR signaling.
authors: Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212;
authors: Nicholas P
authors: 0000-0003-4614-5996
authors: NP
authors: Goplen
authors: Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212;
authors: Vikas
authors: 0000-0003-4816-4875
authors: V
authors: Saxena
authors: Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212;
authors: Karin M
authors: KM
authors: Knudson
authors: Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905; and.
authors: Adam G
authors: AG
authors: Schrum
authors: Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905; and.
authors: Diana
authors: D
authors: Gil
authors: Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212;
authors: Mark A
authors: MA
authors: Daniels
authors: Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, Ashworth Laboratories, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom.
authors: Rose
authors: 0000-0001-9816-2638
authors: R
authors: Zamoyska
authors: Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO 65212; teixeiropernase@missouri.edu.
authors: Emma
authors: 0000-0002-3596-5481
authors: E
authors: Teixeiro
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000276:immunology / Q000378:metabolism; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; C491468:Fyb protein, mouse; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011948:Receptors, Antigen, T-Cell; D018664:Interleukin-12; D007371:Interferon-gamma