IL-12 signals through the TCR to support CD8 innate immune responses

Nicholas P. Goplen, Vikas Saxena, Karin M. Knudson, Adam G. Schrum, Diana Gil, Mark A. Daniels, Rose Zamoyska, Emma Teixeiro*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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-g 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.

Original languageEnglish
Pages (from-to)2434-2443
Number of pages10
JournalThe Journal of Immunology
Issue number6
Early online date13 Jul 2016
Publication statusPublished - 15 Sept 2016


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