TY - JOUR
T1 - Tc17 cells are capable of mediating immunity to vaccinia virus by acquisition of a cytotoxic phenotype
AU - Yeh, Norman
AU - Glosson, Nicole L.
AU - Wang, Nan
AU - Guindon, Lynette
AU - McKinley, Carl
AU - Hamada, Hiromasa
AU - Li, Qingsheng
AU - Dutton, Richard W.
AU - Shrikant, Protul
AU - Zhou, Baohua
AU - Brutkiewicz, Randy R.
AU - Blum, Janice S.
AU - Kaplan, Mark H.
PY - 2010/8/15
Y1 - 2010/8/15
N2 - CD8 T cells can acquire cytokine-secreting phenotypes paralleling cytokine production from Th cells. IL-17-secreting CD8 T cells, termed Tc17 cells, were shown to promote inflammation and mediate immunity to influenza. However, most reports observed a lack of cytotoxic activity by Tc17 cells. In this study, we explored the anti-viral activity of Tc17 cells using a vaccinia virus (VV) infection model. Tc17 cells expanded during VV infection, and TCR transgenic Tc17 cells were capable of clearing recombinant VV infection. In vivo, adoptively transferred Tc17 cells lost the IL-17-secreting phenotype, even in the absence of stimulation, but they did not acquire IFN-γ-secreting potential unless stimulated with a virus-encoded Ag. However, examination of cells following infection demonstrated that these cells acquired cytotoxic potential in vivo, even in the absence of IFN-γ. Cytotoxic potential correlated with Fasl expression, and the cytotoxic activity of postinfection Tc17 cells was partially blocked by the addition of anti-FasL. Thus, Tc17 cells mediate VV clearance through expression of specific molecules associated with cytotoxicity but independent of an acquired Tc1 phenotype.
AB - CD8 T cells can acquire cytokine-secreting phenotypes paralleling cytokine production from Th cells. IL-17-secreting CD8 T cells, termed Tc17 cells, were shown to promote inflammation and mediate immunity to influenza. However, most reports observed a lack of cytotoxic activity by Tc17 cells. In this study, we explored the anti-viral activity of Tc17 cells using a vaccinia virus (VV) infection model. Tc17 cells expanded during VV infection, and TCR transgenic Tc17 cells were capable of clearing recombinant VV infection. In vivo, adoptively transferred Tc17 cells lost the IL-17-secreting phenotype, even in the absence of stimulation, but they did not acquire IFN-γ-secreting potential unless stimulated with a virus-encoded Ag. However, examination of cells following infection demonstrated that these cells acquired cytotoxic potential in vivo, even in the absence of IFN-γ. Cytotoxic potential correlated with Fasl expression, and the cytotoxic activity of postinfection Tc17 cells was partially blocked by the addition of anti-FasL. Thus, Tc17 cells mediate VV clearance through expression of specific molecules associated with cytotoxicity but independent of an acquired Tc1 phenotype.
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U2 - 10.4049/jimmunol.1000818
DO - 10.4049/jimmunol.1000818
M3 - Article
C2 - 20624947
AN - SCOPUS:77956944306
SN - 0022-1767
VL - 185
SP - 2089
EP - 2098
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -