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An important role of Tyk2 in APC function of dendritic cells for priming CD8 + T cells producing IFN‐γ
Author(s) -
Aizu Keiji,
Li Wei,
Yajima Toshiki,
Arai Toshiyuki,
Shimoda Kazuya,
Nimura Yuji,
Yoshikai Yasunobu
Publication year - 2006
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200636173
Subject(s) - biology , cytotoxic t cell , adoptive cell transfer , cd8 , mhc class i , priming (agriculture) , tyrosine kinase 2 , t cell , mhc class ii , immunology , microbiology and biotechnology , immune system , receptor , in vitro , biochemistry , botany , germination , platelet derived growth factor receptor , growth factor
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 (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 + 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.