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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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-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 (US)
Pages (from-to)2434-2443
Number of pages10
JournalJournal of Immunology
Volume197
Issue number6
DOIs
StatePublished - Sep 15 2016

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Interleukin-12
Innate Immunity
T-Lymphocytes
Peptides
Cytokines
Cytokine Receptors
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Goplen, N. P., Saxena, V., Knudson, K. M., Schrum, A. G., Gil, D., Daniels, M. A., ... Teixeiro, E. (2016). IL-12 signals through the TCR to support CD8 innate immune responses. Journal of Immunology, 197(6), 2434-2443. https://doi.org/10.4049/jimmunol.1600037

IL-12 signals through the TCR to support CD8 innate immune responses. / Goplen, Nicholas P.; Saxena, Vikas; Knudson, Karin M.; Schrum, Adam G.; Gil, Diana; Daniels, Mark A.; Zamoyska, Rose; Teixeiro, Emma.

In: Journal of Immunology, Vol. 197, No. 6, 15.09.2016, p. 2434-2443.

Research output: Contribution to journalArticle

Goplen, NP, Saxena, V, Knudson, KM, Schrum, AG, Gil, D, Daniels, MA, Zamoyska, R & Teixeiro, E 2016, 'IL-12 signals through the TCR to support CD8 innate immune responses', Journal of Immunology, vol. 197, no. 6, pp. 2434-2443. https://doi.org/10.4049/jimmunol.1600037
Goplen NP, Saxena V, Knudson KM, Schrum AG, Gil D, Daniels MA et al. IL-12 signals through the TCR to support CD8 innate immune responses. Journal of Immunology. 2016 Sep 15;197(6):2434-2443. https://doi.org/10.4049/jimmunol.1600037
Goplen, Nicholas P. ; Saxena, Vikas ; Knudson, Karin M. ; Schrum, Adam G. ; Gil, Diana ; Daniels, Mark A. ; Zamoyska, Rose ; Teixeiro, Emma. / IL-12 signals through the TCR to support CD8 innate immune responses. In: Journal of Immunology. 2016 ; Vol. 197, No. 6. pp. 2434-2443.
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