Retinal antigen-specific regulatory T cells protect against spontaneous and induced XXXX and require local dendritic cells.

@entity20829 @entity19 @entity25948 @entity11805 @entity4643 @entity3744 @entity792
BACKGROUND: We previously reported that the peripheral regulatory T cells (pTregs) generated 'on-demand' in the retina were crucial to retinal immune privilege, and in vitro analysis of retinal dendritic cells (DC) showed they possessed antigen presenting cell (APC) activity that promoted development of the Tregs and effector T cells (Teffs). Here, we expanded these findings by examining whether locally generated, locally acting pTregs were protective against spontaneous @entity792 and @entity792 mediated by @entity25948 ( @entity25948 ). We also examined the APC capacity of retinal DC in vivo. METHODS: Transgenic (Tg) @entity19 expressing @entity20829 ( @entity20829 ) and/or green fluorescent protein (GFP) under control of the endogenous @entity3744 promoter (GFP only in FG @entity19 , GFP and @entity20829 in FDG @entity19 ) or the @entity11805 promoter (GFP and @entity20829 in CDG @entity19 ) were used in conjunction with Tg @entity19 expressing beta-galactosidase (bgal) as retinal neo-self antigen and bgal-specific TCR Tg @entity19 (BG2). Retinal T cell responses were assayed by flow cytometry and retinal @entity792 assessed by histological examination. RESULTS: Local depletion of the Tregs enhanced actively induced experimental autoimmune @entity4643 to the highly expressed retinal self-antigen @entity25948 in FDG @entity19 and spontaneous @entity792 in bgal-FDG-BG2 @entity19 , but not in @entity19 lacking autoreactive T cells or their target antigen in the retina. The presence of retinal bgal downregulated the generation of antigen-specific Teffs and pTregs within the retina in response to local bgal challenge. Retinal DC depletion prevented generation of Tregs and Teffs within retina after bgal injection. Microglia remaining after DC depletion did not make up for loss of DC-dependent antigen presentation. CONCLUSIONS: Our results suggest that local retinal Tregs protect against spontaneous organ-specific @entity792 and that T cell responses within the retina require the presence of local DC.
