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J. Schwartzkopff, S. Sugita, T.F. Ng, J.W. Streilein; CTLA–4+ CD8+ T cells that encounter B7.2+ iris pigment epithelial cells express their own B7.2 to achieve global suppression of T cell activation . Invest. Ophthalmol. Vis. Sci. 2004;45(13):588.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The pigment epithelium (PE) as part of the blood–ocular barrier has developed mechanisms by which an overwhelming immune response can be regulated. In particular, B7.2+ iris pigment epithelial (IPE) cells suppress naïve T cell activation in vitro by directly interacting with CTLA–4 on T cells. Since only a few naïve T cells express CTLA–4 on their surface yet virtually all T cells are suppressed globally in co–cultures with IPE, we have investigated the mechanisms by which this effect is achieved. Methods: IPE cells and splenic T cells were derived from C57BL/6 mice and mice deficient in B7.1, B7.2, CTLA–4 and/or CD28. T cells were activated with anti–CD3 mAb in the presence of IPE, and proliferation of CD4+ and CD8+ T cell subsets was assayed by loss of CFSE intensity or [3H]–thymidine incorporation. Surface expression of CD28, CTLA–4 and B7.2 on T cells and IPE was evaluated by FACS or immunohistochemistry. The amount of cytokines in culture supernatants was measured by ELISA (IFN–γ, IL–2, IL–4, IL–10) or by bioassay (TGF–ß). Results: In co–cultures with IPE, proliferation of all CD4+ and the majority of CD8+ T cells was profoundly suppressed. However, a small fraction of CTLA–4+ CD8+ T cells divided five times, became B7.2+, secreted enhanced amounts of active TGF–ß, and acquired the characteristics of a regulatory T cell. Regulators of this type failed to develop if either T cells or IPE were obtained from B7.2 deficient mice. Conclusions: A CTLA–4+ CD8+ T cell subset responds to B7.2+ IPE by becoming T regulators that utilize their own expression of B7.2 to suppress bystander CD4+ and CD8+ T cells. Cells of this type may modulate the expression of immunogenic inflammation within the eye, thus preserving the integrity of the visual axis.
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