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A. Amadi-Obi, C.-R. Yu, H.-M. Oh, C. E. Egwuagu; STAT3 Inhibits Proliferation of CD4+ T Cells and Promotes Their Survival. Invest. Ophthalmol. Vis. Sci. 2010;51(13):814.
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© ARVO (1962-2015); The Authors (2016-present)
T cell mediated adaptive immune responses play a central role in autoimmunity. Thus understanding the mechanisms that regulate T cell activation and survival are central to the design of therapeutic intervention in autoimmune diseases such as uveitis and multiple sclerosis. Mice with conditional deletion of STAT3 (signal transducer and activator of transcription-3) in T cells (STAT3KO) exhibit aberrant proliferative response to IRBP and do not develop EAU or EAE. In this study we have used STAT3KO mice to dissect the role of STAT3 in T cell activation, survival and effector functions.
CD4 T cells were isolated from wild type (WT) and STAT3KO and cultured with anti-CD3/anti-CD28. Proliferation of WT and STAT3KO T cells was assessed by CFSE dilution assay and flow cytometry. Total RNA and whole cell extracts isolated from naïve or activated T cells were analyzed by western blot or PCR assays.
We observed marked increase in the proliferative capacity of STAT3KO T cells, suggesting that STAT3 negatively regulates lymphocyte proliferation by modulating cell cycle regulatory proteins. In addition STAT3KO cells exhibit higher levels of apoptosis, resulting from decrease in expression of pro-apoptotic proteins.
Our data suggest that suppressive effect of STAT3 on T cell proliferation can be exploited in the treatment of lymphoproliferative and autoimmune diseases
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