title: Functional Conversion and Dominance of γδ T Subset in Mouse Experimental Autoimmune Uveitis.
abstract: We have previously shown that activated γδ T cells have a much stronger proinflammatory effect in the development of experimental autoimmune uveitis than their nonactivated counterparts. Our present study explored γδ T cell subsets are functionally distinct in autoimmune pathogenesis and determined the pathogenic contribution of biased Vγ4+γδ T cell activation in this disease. By systematically comparing two major peripheral γδ T cell subsets, the Vγ1+and the Vγ4+cells, we found that the Vγ4+cells were readily activated in B6 mice during experimental autoimmune uveitis development, whereas Vγ1+cells remained nonactivated. Cytokines that were abundantly found in the serum of immunized mice activated Vγ4+, but did not activate Vγ1+, cells. The Vγ4+cells had a strong proinflammatory activity, whereas the Vγ1+cells remained nonactivated when tested immediately after isolation from immunized mice. However, when the Vγ1+cells were activated in vitro, they promoted inflammation. Our results demonstrated that activation is a major factor in switching the enhancing and inhibiting effects of both Vγ1+and Vγ4+γδ T cell subsets, and that γδ T cell subsets differ greatly in their activation requirements. Whether the enhancing or inhibiting function of γδ T cells is dominant is mainly determined by the proportion of the γδ T cells that are activated versus the proportion not activated.
authors.affiliation: Doheny Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90033.
authors.forename: Dongchun
authors.initials: D
authors.lastname: Liang
authors.affiliation: Tianjin Medical University Eye Hospital, Eye Institute and School of Optometry and Ophthalmology, Tianjin 300384, China; and.
authors.forename: Hong
authors.identifier: 0000-0002-9983-3410
authors.initials: H
authors.lastname: Nian
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202.
authors.forename: Hui
authors.initials: H
authors.lastname: Shao
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Kaplan
authors.affiliation: Doheny Eye Institute, Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90033; dsun@doheny.org.
authors.forename: Deming
authors.identifier: 0000-0003-4851-0416
authors.initials: D
authors.lastname: Sun
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000503:physiopathology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014605:Uveitis / Q000276:immunology*
chemical_list: D016207:Cytokines; D016692:Receptors, Antigen, T-Cell, gamma-delta