IL-12 Signals through the TCR To Support CD8 Innate Immune Responses

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...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2016-09, Vol.197 (6), p.2434-2443
Main Authors: Goplen, Nicholas P, Saxena, Vikas, Knudson, Karin M, Schrum, Adam G, Gil, Diana, Daniels, Mark A, Zamoyska, Rose, Teixeiro, Emma
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - deficiency
Adaptor Proteins, Signal Transducing - immunology
Adaptor Proteins, Signal Transducing - metabolism
Animals
CD8-Positive T-Lymphocytes - immunology
Cytokines - immunology
Cytokines - metabolism
Cytotoxicity, Immunologic
Immunity, Innate
Interferon-gamma - genetics
Interferon-gamma - immunology
Interleukin-12 - immunology
Interleukin-12 - metabolism
Lymphocyte Activation
Mice
NK Cell Lectin-Like Receptor Subfamily K - genetics
NK Cell Lectin-Like Receptor Subfamily K - immunology
Protein Binding - immunology
Receptors, Antigen, T-Cell - genetics
Receptors, Antigen, T-Cell - immunology
Receptors, Antigen, T-Cell - metabolism
Signal Transduction
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1600037