Retinal pigment epithelial cells induce foxp3(+) regulatory T cells via membrane-bound TGF-β.
OBJECTIVE
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.
Vega
Jose L
JL
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Saban
Daniel
D
Carrier
Yejun
Y
Masli
Sharmila
S
Weiner
Howard L
HL
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000172:deficiency; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D055213:Retinal Pigment Epithelium / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism* / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053773:Transforming Growth Factor beta1