title: Tc17 cells are capable of mediating immunity to vaccinia virus by acquisition of a cytotoxic phenotype.
abstract: 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-gamma-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-gamma. 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.
authors.affiliation: Department of Microbiology and Immunology, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Norman
authors.initials: N
authors.lastname: Yeh
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Glosson
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Lynette
authors.initials: L
authors.lastname: Guindon
authors.forename: Carl
authors.initials: C
authors.lastname: McKinley
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Hamada
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Li
authors.forename: Richard W
authors.initials: RW
authors.lastname: Dutton
authors.forename: Protul
authors.initials: P
authors.lastname: Shrikant
authors.forename: Baohua
authors.initials: B
authors.lastname: Zhou
authors.forename: Randy R
authors.initials: RR
authors.lastname: Brutkiewicz
authors.forename: Janice S
authors.initials: JS
authors.lastname: Blum
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007109:Immunity / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014615:Vaccinia / Q000276:immunology* / Q000821:virology; D014616:Vaccinia virus / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: D020381:Interleukin-17; D011948:Receptors, Antigen, T-Cell; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D018664:Interleukin-12; D007371:Interferon-gamma