HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) A correction has been published Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sugita, S. Articles by Streilein, J. W. Search for Related Content PubMed PubMed Citation Articles by Sugita, S. Articles by Streilein, J. W.

B7⁺ Iris Pigment Epithelium Induce CD8⁺ T Regulatory Cells; Both Suppress CTLA-4⁺ T Cells^1,2

Sunao Sugita^*,, Tat Fong Ng^*, Philip J. Lucas, Ronald E. Gress and J. Wayne Streilein^3,*

^* Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114; Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and Department of Ophthalmology & Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan

Ocular pigment epithelia contribute to immune privilege by suppressing T cell activation and converting T cells into regulatory T regulatory cells (Tregs) that inhibit bystander T cell activation. Iris pigment epithelium (IPE) does so through direct cell-cell contact with naive T cells, and this suppressive contact is via interactions between B7 expressed constitutively on IPE cells and CTLA-4 expressed on a subpopulation of CD8⁺ T cells. We have now examined whether TGF is required in this process. We report that IPE produces both soluble and membrane-bound active TGF, but that only the latter is actually delivered to CD8⁺ T cells. In turn, these T cells become IPE Tregs by up-regulating their own expression of B7-1/B7-2 and soluble and membrane-bound TGF. IPE Tregs through their expression of B7 are able to engage CTLA-4⁺ bystander T cells, and thus precisely, target delivery of membrane-bound TGF. We propose that this mechanism of suppression via TGF ensures that soluble active TGF is not released into the ocular microenvironment where it can have unregulated and deleterious effects, including elevation of intraocular pressure and development of glaucoma.

This article has been cited by other articles:

				Y. Futagami, S. Sugita, J. Vega, K. Ishida, H. Takase, K. Maruyama, H. Aburatani, and M. Mochizuki Role of Thrombospondin-1 in T Cell Response to Ocular Pigment Epithelial Cells J. Immunol., June 1, 2007; 178(11): 6994 - 7005. [Abstract] [Full Text] [PDF]

				J. Stein-Streilein and A. W. Taylor An eye's view of T regulatory cells J. Leukoc. Biol., March 1, 2007; 81(3): 593 - 598. [Abstract] [Full Text] [PDF]

				S. Sugita, H. Keino, Y. Futagami, H. Takase, M. Mochizuki, J. Stein-Streilein, and J. W. Streilein B7+ Iris Pigment Epithelial Cells Convert T Cells into CTLA-4+, B7-Expressing CD8+ Regulatory T Cells Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5376 - 5384. [Abstract] [Full Text] [PDF]