Retinal Pigment Epithelial Cells Induce foxp3⁺ Regulatory T Cells via Membrane-bound TGF-β

Abstract

Purpose: It is speculated that retinal pigment epithelial (RPE) cells convert naïve T cells into regulatory T cells (Tregs) via soluble factors such as transforming growth factor beta (TGF-β). Yet presence or absence of similar membrane-bound mechanisms on RPE cells has yet to be addressed. Here the authors investigated the expression of surface TGF-β by RPE cells and its participation in the conversion of naive T cells into Tregs.

Methods: They examined the phenotype of murine CD4⁺ CD25⁻ T cells activated in the presence of ethanol-fixed RPE cell layers as fixation preserves membrane structure while preventing the secretion of soluble factors.

Results: Fixed RPE cells supported the development of a de novo foxp3⁺ Th3-like suppressor phenotype in activated peripheral naïve T cells through an interaction that required both RPE-derived surface TGF-β, and T-cell derived TGF-β1.

Conclusions: Aside from soluble factors, RPE-derived surface TGF-β can convert activated naïve T cells into Tregs.

KEYWORDS::

• astrocytes
• foxp3
• regulatory T cells
• retinal pigment epithelium
• TGF-beta

ACKNOWLEDGMENTS

This work was supported in part by a grant from the National Institute of Allergy and Infectious Diseases, NIAID, 1F32AI066677-01 to JLV.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.