EVIDENCE FOR SELECTIVE ACCUMULATION OF V-BETA-8-LYMPHOCYTES IN EXPERIMENTAL AUTOIMMUNE UVEORETINITIS INDUCED WITH 2 DIFFERENT RETINAL ANTIGENS( T)

Experimental autoimmune uveoretinitis (EAU) is a T cell-mediated autoi mmune disease that serves as a model of human intraocular inflammatory disease (uveitis) and is initiated in susceptible animals by immuniza tion with retinal Ag, such as interphotoreceptor retinoid binding prot ein (IRBP) and S-Ag (SAg). Previous studies of TCR usage by uveitogeni c T cells suggested a possible connection between pathogenicity of T l ymphocytes and usage of Vbeta8 family genes. Here, we have analyzed th e T cell repertoire at the autoimmune site by examining Vbeta gene exp ression in the retinas of rats with SAg- or IRBP-induced uveitis. Our data show the following: 1) T cell response to SAg or IRBP is clonally heterogeneous: at least 15 of the 20 known rat TCR families were dete cted in the retinas of rats with EAU. 2) Vbeta8+ T cells were selectiv ely increased in retina during the early stage of EAU, and the pattern of Vbeta8 subfamily member utilization in the retina was Ag-dependent : Vbeta8.2+ and Vbeta8.3+ T cells were found in the retina of rats imm unized with IRBP but only Vbeta8.2+ cells in SAg-induced EAU. Vbeta8.1 cells were not detected in any of the samples. 3) Kinetic change in t he proportions of Vbeta8.2+ and Vbeta8.3+ T cells was observed in IRBP -EAU: on the day of clinical onset of disease, Vbeta8.3+ cells were th e only member of the Vbeta8 family detected, but 24 h later, Vbeta8.2 T cells appeared and became the dominant Vbeta8 clonotype in the reti na. 4) The pattern of Vbeta8 family member usage by T cells in uveitog enic lines specific to the corresponding Ag was similar to their utili zation in the uveitic response in the retina. DNA sequence analysis of 75 Vbeta8 cDNA clones from uveitogenic T cell lines revealed that, of 20 Vbeta8 clones isolated from SAg-specific T cell lines, all were Vb eta8.2 TCR, whereas among 55 Vbeta8 clones from IRBP-specific lines, 3 6 were Vbeta8.2 and 19 were Vbeta8.3. In similarity to the retina, no Vbeta8.1+ T cells were detected from these T cell lines. Taken togethe r, our data suggest a bias towards usage of Vbeta8+ cells in EAU and, depending on the autoantigen mediating the disease, particular Vbeta8 subfamily member(s) were preferentially utilized or excluded from the autoimmune response.