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B. Matta, P. Jha, P. S. Bora, N. S. Bora; Role of T Effector and CD4+CD25+FoxP3+ T Regulatory Cells in Idiopathic Anterior Uveitis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4843.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the role of T effector and CD4+CD25+FoxP3+ T regulatory cells in the pathogenesis of idiopathic anterior uveits (AU).
Patients diagnosed with idiopathic anterior uveitis (AU) at Jones Eye Institute, University of Arkansas for Medical Sciences (Little Rock, AR) were divided into two groups - patients with clinically active AU and patients with clinically inactive AU. Subjects with no history of eye disease were used as control. Peripheral blood mononuclear cells (PBMCs) isolated from the patients and control subjects were cultured in presence of bovine melanin-associated antigen (MAA). Flow cytometry was used to examine the proliferative response of CFSE stained CD3+ Tcells to MAA and to determine the percentage of CD4+CD25+FoxP3+ Tregs. In another set of experiments, total MLCs or CD4+CD25+ Tregs purified from the popliteal lymph nodes of tolerized donor animals were adoptively transferred to Lewis rats with already existing EAAU. EAAU was monitored in these animals both clinically and histologically.
CD3+ T cells from the patients with active idiopathic AU proliferated at a significantly higher rate in presence of MAA compared to the CD3+ T cells from control donors and patients with inactive AU. Interestingly, flow cytometric analysis demonstrated that the percentage of CD4+CD25+FoxP3+ T regs was significantly less in the patients with active AU compared to control subjects and patients with inactive AU. Adoptive transfer of total MLCs as well as CD4+CD25+ Tregs harvested from the popliteal lymph nodes of tolerized donor Lewis rats to recipient animals with ongoing EAAU resulted in a sharp decline in the disease activity and early resolution of EAAU.
T cells recognizing MAA are present in the blood of patients with active AU indicating that MAA may be the autoantigen for human idiopathic AU as well. Percentage of CD4+CD25+ FoxP3+ Tregs was significantly reduced in patients with active AU and Tregs can be used to inhibit ocular inflammation in the animals with already existing EAAU.
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