Tyk2 signaling in host environment plays an important role in contraction of antigen-specific CD8+ T cells following a microbial infection.
Tyrosine kinase 2 (Tyk2), a member of JAK signal transducer family contributes to the signals triggered by IL-12 for IFN-gamma 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 OVA(257-264)/K(b) 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-gamma 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-gamma production in host environment plays an important role in contraction of effector CD8+ T cells following a microbial infection.
Li
Wei
W
Division of Host Defense and Digital Medicine Initiative, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan.
Yamada
Hisakata
H
Yajima
Toshiki
T
Nakagawa
Ryusuke
R
Shimoda
Kazuya
K
Nakayama
Keiichi
K
Yoshikai
Yasunobu
Y
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D053148:Caspase 3 / Q000378:metabolism; D048429:Cell Size; D007371:Interferon-gamma / Q000378:metabolism; D007700:Kinetics; D008089:Listeria monocytogenes / Q000254:growth & development; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D053634:TYK2 Kinase / Q000235:genetics / Q000502:physiology*
C110366:OVA-8; D010446:Peptide Fragments; D007371:Interferon-gamma; D010047:Ovalbumin; D053634:TYK2 Kinase; C499356:Tyk2 protein, mouse; D053148:Caspase 3