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Anti-TNFalpha therapy modulates the phenotype of peripheral blood CD4+ T cells in patients with posterior segment intraocular inflammation.

Abstract：

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)-alpha induces suppression of Th1 cells, macrophage activation, and target organ damage. Previous studies implicated an efficacy of anti-TNFalpha therapies in patients with PSII. This study investigated the immunomodulatory effect of anti-TNFalpha 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 TNFalpha 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]-gamma, interleukin [IL]-10, and TNFalpha) 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 IFNgamma-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 TNFalpha activity in PSII increases the fraction of peripheral blood CD4+ T cells expressing IL-10, which correlates with a recovery of visual function.

journal_name

Invest Ophthalmol Vis Sci

journal_title

Investigative ophthalmology & visual science

authors

Greiner K,Murphy CC,Willermain F,Duncan L,Plskova J,Hale G,Isaacs JD,Forrester JV,Dick AD

doi

10.1167/iovs.03-0659

keywords:

subject

Has Abstract

pub_date

2004-01-01 00:00:00

pages

170-6

issue

eissn

0146-0404

issn

1552-5783

journal_volume

pub_type

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Anti-TNFalpha therapy modulates the phenotype of peripheral blood CD4+ T cells in patients with posterior segment intraocular inflammation.