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A. W. Taylor, C. H. Lau; Functional Mechanisms of Retinal Induced Suppressive Macrophages. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3624.
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Previously we have shown that retinal pigmented epithelial cells (RPE) contribute factors into the ocular microenvironment that promote anti-inflammatory activity in activated macrophages. Cytokines from RPE of healthy eyes suppress IL-1ß and TNF-α production, and induced IL-10, nitric oxide and Arginase1 production by LPS-activated macrophages. This finding suggests that the RPE mediates the activation of suppressor macrophages; therefore, we investigated whether such RPE treated macrophages suppress T cell IFN-γ production and induce apoptosis.
The RPE eyecups from naive C57BL/6 mice were prepared, placed into culture, and incubated for 48 hours. Spleen macrophages of naive mice were prepared and cultured with the RPE eyecup conditioned media with or without LPS. After 24 hours of incubation, the macrophage cultures were washed and primed T cells from draining lymph nodes of mice immunized with Mycobacterium tuberculosis antigen (MtAg) were added to the cultures. Anti-CD3 stimulating antibody (2C11) was then added to the cultures. In some experiments, the treated macrophages were also pulsed with MtAg to activate antigen specific T cells. After incubation the T cells were assayed for apoptosis by TUNEL, and the supernatant was assayed for IFN-γ by ELISA.
The LPS-activated macrophages treated with RPE conditioned media suppressed IFN-γ production by the anti-CD3-stimulated T cells. Apoptosis of anti-CD3 activated T-cell was 30% when co-culture with resting macrophages or 15% when co-culture with LPS-activated macrophages, but apoptosis was significantly lower, 2%, when co-culture with RPE condition media treated LPS-activated macrophages. Also, the LPS-activated macrophages treated with RPE conditioned media suppressed IFN-γ production by T cells under antigen specific conditions.
RPE promotes suppressive macrophage functionality. This suppression does not require antigen-specificity. However, unlike other suppressor macrophages the RPE-treated macrophages are promoting T cell viability. The implication of these findings is that the ocular microenvironment instead of eliminating immunity promotes selective immune responses for immune privilege.
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