title: An important role of Tyk2 in APC function of dendritic cells for priming CD8+ T cells producing IFN-gamma.
abstract: Tyrosine kinase 2 (Tyk2) contributes to the signals triggered by IL-12 for IFN-gamma 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-gamma production. The numbers of both MHC class Ib (H2-M3)- or MHC class Ia (Kb)-restricted CD8+ T cells producing IFN-gamma 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)/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-gamma. 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.
authors.affiliation: Division of Host Defense, Research Center of Prevention of Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Aizu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yajima
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Arai
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimoda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nimura
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yoshikai
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000201:enzymology / Q000276:immunology; D000942:Antigens, Bacterial / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D008088:Listeriosis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D053634:TYK2 Kinase / Q000235:genetics / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D015234:HLA-A Antigens; D015235:HLA-B Antigens; C110366:OVA-8; D010446:Peptide Fragments; D007371:Interferon-gamma; D010047:Ovalbumin; D053634:TYK2 Kinase; C499356:Tyk2 protein, mouse