Iris pigment epithelium expressing CD86 (B7-2) directly suppresses T cell activation in vitro via binding to cytotoxic T lymphocyte-associated antigen 4.
A monolayer of pigment epithelium (PE) lines the iris PE (IPE), ciliary body PE, and retina PE of the inner eye, an immune-privileged site. These neural crest-derived epithelial cells participate in ocular immune privilege through poorly defined molecular mechanisms. Murine PE cells cultured from different ocular tissues suppress T cell activation by differing mechanisms. In particular, IPE cells suppress primarily via direct cell to cell contact. By examining surface expression of numerous candidate molecules (tumor necrosis factor receptor [TNFR]1, TNFR2, CD36, CD40, CD47, CD80, CD86, PD-L1, CD95 ligand, and type I interferon receptor), we report that IPE cells uniquely express on their surface the costimulatory molecule CD86. When IPE were blocked with anti-CD86 or were derived from CD80/CD86 (but not CD80) knockout (KO) mice, the cells displayed reduced capacity to suppress T cell activation. IPE also failed to suppress activation of T cells in the presence of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) immunoglobulin or if the T cells were obtained from CTLA-4 (but not CD28) KO mice. We conclude that iris pigment epithelial cells constitutively express cell surface CD86, which enables the cells to contact inhibit T cells via direct interaction with CTLA-4. Thus, ocular immune privilege is achieved in part by subversion of molecules that are usually used for conventional immune costimulation.
Sugita
Sunao
S
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Streilein
J Wayne
JW
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology*; D018122:B7-1 Antigen / Q000502:physiology; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010857:Pigment Epithelium of Eye / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D016207:Cytokines; D008562:Membrane Glycoproteins