Association between immune recovery uveitis and a diverse intraocular cytomegalovirus-specific cytotoxic T cell response

Cytomegalovirus (CMV) causes serious infection in individuals with deficient T cell immunity. In acquired immunodeficiency syndrome, the retina is a major site of progressive infection, despite the availability of therapy that targets CMV. The administration of highly active antiretroviral therapy to suppress human immunodeficiency virus frequently results in resolution of CMV retinitis, but this may be complicated by ocular inflammation termed "immune recovery uveitis" (IRU). To provide insight into the pathogenesis of IRU, the phenotype and specificity of intraocular T cells in a single patient were analyzed. The T cell infiltrate consisted of a diverse population of CD8(+) CMV-specific T cells, but only a minority of these T cells recognized the CMV phosphoprotein 65 and immediate early protein 1, which have been considered major targets of the host response. These results imply that reconstitution of CMV-specific T cells plays a role in IRU and suggest that the specificity of T cells engaged in the control of CMV at local sites of reactivation may be broad.