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Therapy Modulates the Phenotype of Peripheral Blood CD4+ T Cells in Patients with Posterior Segment Intraocular Inflammation
1From the Department of Ophthalmology, University of Aberdeen, Aberdeen, United Kingdom; the 3Division of Ophthalmology, University of Bristol, Bristol, United Kingdom; the 4Therapeutic Antibody Centre, University of Oxford, Oxford, United Kingdom; and the 5Department of Rheumatology, School of Clinical Medical Sciences, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, United Kingdom.
PURPOSE. Posterior segment intraocular inflammation (PSII) is a putative Th1 CD4+ cell mediated autoimmune disorder. In experimental autoimmune uveoretinitis, neutralization of tumor necrosis factor (TNF)-
induces suppression of Th1 cells, macrophage activation, and target organ damage. Previous studies implicated an efficacy of anti-TNF therapies in patients with PSII. This study investigated the immunomodulatory effect of anti-TNF therapy to find predictors of effective immunosuppression in PSII.
METHODS. Fifteen patients with PSII refractory to conventional immunosuppressive therapy received a single infusion of a recombinant protein generated by fusing the p55 TNF receptor with human IgG1. During 17 treatment periods, visual acuity (logarithm of the minimum angle of resolution [logMAR]) was monitored as a response criterion. Phenotype markers of CD4+ T cells were analyzed before and 2, 4, and 12 weeks after therapy. Expression of intracellular cytokines (interferon [IFN]-
, interleukin [IL]-10, and TNF) and Th1/Th2-specific chemokine receptors (CXCR3, CCR4, and CCR5) on peripheral blood CD4+ T cells was determined using flow cytometry.
RESULTS. The fraction of IL-10–expressing CD4+ T cells was increased during 12 of 17 treatment periods within 2 weeks after treatment. During eight treatment periods, this increase was associated with an improvement of visual acuity of at least 0.2 logMAR within 4 weeks (P = 0.029). The ratio between IL-10- and IFN-expressing CD4+ T cells was significantly increased 2 weeks after therapy (P = 0.015). There was no significant change of CXCR3, CCR4, or CCR5 expression.
CONCLUSIONS. Neutralizing TNF activity in PSII increases the fraction of peripheral blood CD4+ T cells expressing IL-10, which correlates with a recovery of visual function.
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