Tyrosine kinase 2 (Tyk2), a member of JAK signal transducer family contributes to the signals triggered by IL-12 for IFN-γ production. To elucidate potential roles of Tyk2 in generation and maintenance of Ag-specific CD8+ T cells, we followed the fate of OVA-specific CD8+ T cells in Tyk2-deficient (-/-) mice after infection with recombinant Listeria monocytogenes expressing OVA (rLM-OVA). Results showed that the numbers of OVA257-264/Kb tetramer-positive CD8+ T cells in Tyk2-/- mice were almost the same as those in Tyk2+/+ mice at the expansion phase on day 7 but were significantly larger in Tyk2 -/- mice than those in Tyk2+/+ mice at the contraction phase on day 10 and at the memory phase on day 60 after infection. The intracellular expression level of active caspase-3 was significantly decreased in the OVA-specific CD8+ T cells of Tyk2-/- mice on day 7 compared with those of Tyk2+/+ mice. Adaptive transfer experiments revealed that Tyk2 signaling in other factors rather than CD8+ T cells played a regulatory role in CD8+ T cell contraction following infection. Administration of exogenous IFN-γ from day 6 to day 9 restored the CD8+ T cell contraction in Tyk2-/- mice after infection with rLM-OVA. These results suggest that Tyk2 signaling for IFN-γ production in host environment plays an important role in contraction of effector CD8+ T cells following a microbial infection.
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