Functional Conversion and Dominance of {gamma}{delta} T Subset in Mouse Experimental Autoimmune Uveitis [AUTOIMMUNITY]

We have previously shown that activated T cells have a much stronger proinflammatory effect in the development of experimental autoimmune uveitis than their nonactivated counterparts. Our present study explored T cell subsets are functionally distinct in autoimmune pathogenesis and determined the pathogenic contribution of biased V4⁺ T cell activation in this disease. By systematically comparing two major peripheral T cell subsets, the V1⁺ and the V4⁺ cells, we found that the V4⁺ cells were readily activated in B6 mice during experimental autoimmune uveitis development, whereas V1⁺ cells remained nonactivated. Cytokines that were abundantly found in the serum of immunized mice activated V4⁺, but did not activate V1⁺, cells. The V4⁺ cells had a strong proinflammatory activity, whereas the V1⁺ cells remained nonactivated when tested immediately after isolation from immunized mice. However, when the V1⁺ 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 V1⁺ and V4⁺ T cell subsets, and that T cell subsets differ greatly in their activation requirements. Whether the enhancing or inhibiting function of T cells is dominant is mainly determined by the proportion of the T cells that are activated versus the proportion not activated.

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