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Nalini S Bora, Bharati Matta, Purushottam Jha, Puran S Bora, Immunology; CD4+CD25+FoxP3+ T regulatory cells in experimental autoimmune anterior uveitis. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5297.
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© ARVO (1962-2015); The Authors (2016-present)
To explore the role of CD4+CD25+FoxP3+ T regulatory cells (Tregs) in experimental autoimmune anterior uveitis (EAAU).
Male Lewis rats injected with melanin associated antigen (MAA) were sacrificed at different time points and lymphocytes were purified from the eyes. For the detection of Tregs, lymphocytes were first surface stained with anti CD4-APC and anti CD25-PE. Cells were then intra-cellularly stained with FITC labeled FoxP3 antibody. The percentage of Tregs was determined by flow cytometry. Effect of TGFβ2 on the proliferation of CD4+ T cells harvested from popliteal lymph nodes (LNs) in response to MAA was determined by CFSE cell proliferation assay. MAA sensitized Lewis rats were injected with recombinant TGFβ2 intravenously via the tail vein at days 15, 16 and 17 post-immunization and days -1, 0 and 1 post-immunization separately to study the effect of TGFβ2 on EAAU. Effect of Tregs on on-going EAAU was investigated by adoptive transfer of Tregs purified from LNs of rats tolerized against MAA.
Our results demonstrate that the percentage of CD4+CD25+FoxP3+ Tregs in the eye peaked during the resolution of EAAU. TGFβ2 when injected at the onset of EAAU reduced the severity and duration of the disease. EAAU failed to develop in animals injected with TGFβ2 at the time of immunization. Treatment with TGFβ2 in vitro inhibited the proliferation of CFSE labeled CD4+T cells in response to MAA. Increased percentage of CD4+CD25+FoxP3+ Tregs was noted in MAA-sensitized Lewis rats injected intravenously with TGF-β2. Adoptive transfer of Tregs in the rats with on-going EAAU resulted in sharp decline in disease activity and early resolution of uveitis.
Our data demonstrate that Tregs induced by TGFβ2 inhibited the induction of EAAU. Furthermore, on-going EAAU was suppressed by CD4+CD25+FoxP3+ Tregs. Together, results from present investigation suggest that Tregs play an important role in this model of anterior uveitis.
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