An important role of Tyk2 in APC function of dendritic cells for priming CD8+ T cells producing IFN‐γ

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Abstract
Tyrosine kinase 2 (Tyk2) contributes to the signals triggered by IL‐12 for IFN‐γ production by NK cells and T cells. We found in this study that Tyk2‐deficient (–/–) mice showed increased susceptibility at the early stage after an i.p. infection with Listeria monocytogenes, accompanied by impaired IFN‐γ production. The numbers of both MHC class Ib (H2‐M3)‐ or MHC class Ia (Kb)‐restricted CD8+ T cells producing IFN‐γ and exhibiting cytotoxicity were significantly decreased in Tyk2–/– mice after infection with L. monocytogenes. Using an adoptive transfer system of OT‐I cells expressing OVA257–264/Kb‐specific TCR into Tyk2–/– mice followed by challenge with recombinant L. monocytogenes expressing OVA, we found that the defective Tyk2 signaling in the host environment was at least partially responsible for the impaired CD8+ T cytotoxic‐1 (Tc1) cell responses in Tyk2–/– mice following the infection. Adoptive transfer with MHC class Ib‐ or MHC class Ia‐binding peptide‐pulsed BM‐derived DC from Tyk2–/– mice induced lower levels of the Ag‐specific CD8+ Tc1 cells producing IFN‐γ. These results suggest that Tyk2 signaling is also important for DC function in the induction of MHC class Ia‐ and class Ib‐restricted CD8+ Tc1 cells following L. monocytogenes infection.