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

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 (K^b)-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 OVA_257-264/K^b-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⁺ Tcytotoxic-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.