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Updated: May 12, 2026

In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
Published on: December 30, 2016
Local "on-demand" generation and function of antigen-specific Foxp3+ regulatory T cells
Scott W McPherson1, Neal D Heuss, Dale S Gregerson
1Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA. mcphe003@umn.edu
Abstract:
Extrathymically derived regulatory T cells (iTregs) protect against autoimmunity to tissue-specific Ags. However, whether Ag-specific iTreg generation and function is limited to secondary lymphoid tissue or whether it can occur within the tissue-specific local environment of the cognate Ag remains unresolved. Mice expressing β-galactosidase (βgal) on a retina-specific promoter (βgal mice) in conjunction with mice expressing GFP and diphtheria toxin (DTx) receptor (DTR) under control of the Foxp3 promoter, and βgal-specific TCR transgenic (BG2) mice were used to examine this question. Local depletion (ocular DTx), but not systemic depletion (i.p. DTx), of βgal-specific iTregs enhanced experimental autoimmune uveoretinitis induced by activated βgal-specific effector T cells. Injections of small amounts of βgal into the anterior chamber of the eye produced similar numbers of βgal-specific iTregs in the retina whether the mouse was depleted of pre-existing, circulating Tregs. Taken together, these results suggest that protection from tissue-specific autoimmunity depends on the function of local Ag-specific iTregs and that the retina is capable of local, "on-demand" iTreg generation that is independent of circulating Tregs.
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