title: Vγ4+ T cells regulate host immune response to West Nile virus infection.
abstract: The Vγ4(+) cells, a subpopulation of peripheral γδ T cells, are involved in West Nile virus (WNV) pathogenesis, but the underlying mechanism remains unclear. In this study, we found that WNV-infected Vγ4(+) cell-depleted mice had lower viremia and a reduced inflammatory response in the brain. The Vγ4(+) cells produced IL-17 during WNV infection, but blocking IL-17 signaling did not affect host susceptibility to WNV encephalitis. We also noted that there was an enhanced magnitude of protective splenic Vγ1(+) cell expansion in Vγ4(+) cell-depleted mice compared to that in controls during WNV infection. In addition, Vγ4(+) cells of WNV-infected mice had a higher potential for producing TGF-β. The γδ T cells of WNV-infected Vγ4(+) cell-depleted mice had a higher proliferation rate than those of WNV-infected controls upon ex vivo stimulation with anti-CD3, and this difference was diminished in the presence of TGF-β inhibitor. Finally, Vγ4(+) cells of infected mice contributed directly and indirectly to the higher level of IL-10, which is known to play a negative role in immunity against WNV infection. In summary, Vγ4(+) cells suppress Vγ1(+) cell expansion via TGF-β and increase IL-10 level during WNV infection, which together may lead to higher viremia and enhanced brain inflammation.
authors.affiliation: Department of Microbiology & Immunology, The University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Welte
authors.forename: Judith
authors.initials: J
authors.lastname: Aronson
authors.forename: Bin
authors.initials: B
authors.lastname: Gong
authors.forename: Aparna
authors.initials: A
authors.lastname: Rachamallu
authors.forename: Nicole
authors.initials: N
authors.lastname: Mendell
authors.forename: Robert
authors.initials: R
authors.lastname: Tesh
authors.forename: Slobodan
authors.initials: S
authors.lastname: Paessler
authors.forename: Willi K
authors.initials: WK
authors.lastname: Born
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: O'Brien
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014766:Viremia / Q000276:immunology / Q000821:virology; D014901:West Nile Fever / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D014902:West Nile virus / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016212:Transforming Growth Factor beta; D016753:Interleukin-10
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