Characterization of Toxoplasma gondii-specific T cells recovered from vitreous fluid of patients with ocular toxoplasmosis

PURPOSE. The mechanisms involved in reactivations of latent ocular Toxoplas ma gondii (Tg) infections in immunocompetent patients are poorly understood . In view of the possible role of T cells in the immunopathogenesis of the disease, ocular infiltrating T cells obtained from patients with recurrent ocular toxoplasmosis were characterized phenotypically and ftinctionally. METHODS. Ocular infiltrating T cells were recovered from vitreous fluid (VF ) samples of 10 patients with active recurrent ocular toxoplasmosis. Two pa tients with uveitis of other origins were included as control subjects. T-c ell lines (TCLs) were generated by mitogenic stimulation and tested for rea ctivity to Tg and human retinal protein extracts. The TCLs of three patient s were cloned by limiting dilution. Tg-reactive T-cell clones (TCCs) were c haracterized with respect to their phenotype, T-cell receptor variable (TCR V)-beta gene usage, HLA restriction, and cytokine secretion profile. RESULTS. Reactivity to Tg could be detected only in the TCLS of patients wi th ocular toxoplasmosis. None of the TCLs showed reactivity to human retina l antigens. All tested intraocular Tg-specific TCCs (n = 23) were CD3(+)CD4 (+) and displayed differential TCR V beta usage. Twenty-one TCCs were HLA-D R restricted and two TCCs were restricted by HLA-DP. The majority of the in traocular Tg-specific TCCs showed a bias toward a T-helper (Th)0-Th2 cytoki ne profile. CONCLUSIONS. The data indicate that T cells specific for the triggering mic roorganism infiltrate the eye of patients with recurrent ocular toxoplasmos is. The functional characteristics of the VF-derived Tg-specific T cells an d their presence at the site of inflammation suggest their involvement in t he local inflammatory response of ocular toxoplasmosis.