Functional Conversion and Dominance of γδ T Subset in Mouse Experimental Autoimmune Uveitis.

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.