Limits...
Iris pigment epithelium expressing CD86 (B7-2) directly suppresses T cell activation in vitro via binding to cytotoxic T lymphocyte-associated antigen 4.

Sugita S, Streilein JW - J. Exp. Med. (2003)

Bottom Line: 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.Thus, ocular immune privilege is achieved in part by subversion of molecules that are usually used for conventional immune costimulation.

View Article: PubMed Central - PubMed

Affiliation: Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.

ABSTRACT
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.

Show MeSH

Related in: MedlinePlus

Survey of gene expression of candidate-suppressive cell surface molecules on PE cells cultured from iris, ciliary body, and retina. mRNA was extracted from IPE, CBPE, and RPE cells after 14 d of culture, reverse transcribed, and amplified by PCR. PCR products were electrophoresed in 1, 1.5, and 2% agarose gel and visualized by staining with ethidium bromide.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2196085&req=5

fig2: Survey of gene expression of candidate-suppressive cell surface molecules on PE cells cultured from iris, ciliary body, and retina. mRNA was extracted from IPE, CBPE, and RPE cells after 14 d of culture, reverse transcribed, and amplified by PCR. PCR products were electrophoresed in 1, 1.5, and 2% agarose gel and visualized by staining with ethidium bromide.

Mentions: PE cells were cultured from iris, ciliary body, and retina of eyes of C57BL/6 mice. After 14 d, the cells were harvested and mRNA was extracted. Using RT-PCR, the mRNA of each cell type was probed for transcripts of the following candidate molecules: TNFR1, TNFR2, type I IFNR (IFNα/β receptor), CD95L, CD36, CD40, CD47, CD80 (B7-1), CD86 (B7-2), and PD-L1 (B7-H1). The results of this experiment are presented in Fig. 2. None of the cultured PE cell types expressed the genes for CD95L, CD40, or PD-L1, whereas all of the cell types contained transcripts for TNFR1, TNFR2, type I IFNR, CD36, CD47, and CD80. Only in the case of CD86 did we detect differential expression of transcripts among the three ocular PE cell types. CD86 transcripts were easily detected in cultured IPE and to a lesser extent in CBPE, but not in RPE. Thus, CD86 emerged as a candidate molecule in the suppression of T cell activation achieved by contact exposure to IPE.


Iris pigment epithelium expressing CD86 (B7-2) directly suppresses T cell activation in vitro via binding to cytotoxic T lymphocyte-associated antigen 4.

Sugita S, Streilein JW - J. Exp. Med. (2003)

Survey of gene expression of candidate-suppressive cell surface molecules on PE cells cultured from iris, ciliary body, and retina. mRNA was extracted from IPE, CBPE, and RPE cells after 14 d of culture, reverse transcribed, and amplified by PCR. PCR products were electrophoresed in 1, 1.5, and 2% agarose gel and visualized by staining with ethidium bromide.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196085&req=5

fig2: Survey of gene expression of candidate-suppressive cell surface molecules on PE cells cultured from iris, ciliary body, and retina. mRNA was extracted from IPE, CBPE, and RPE cells after 14 d of culture, reverse transcribed, and amplified by PCR. PCR products were electrophoresed in 1, 1.5, and 2% agarose gel and visualized by staining with ethidium bromide.
Mentions: PE cells were cultured from iris, ciliary body, and retina of eyes of C57BL/6 mice. After 14 d, the cells were harvested and mRNA was extracted. Using RT-PCR, the mRNA of each cell type was probed for transcripts of the following candidate molecules: TNFR1, TNFR2, type I IFNR (IFNα/β receptor), CD95L, CD36, CD40, CD47, CD80 (B7-1), CD86 (B7-2), and PD-L1 (B7-H1). The results of this experiment are presented in Fig. 2. None of the cultured PE cell types expressed the genes for CD95L, CD40, or PD-L1, whereas all of the cell types contained transcripts for TNFR1, TNFR2, type I IFNR, CD36, CD47, and CD80. Only in the case of CD86 did we detect differential expression of transcripts among the three ocular PE cell types. CD86 transcripts were easily detected in cultured IPE and to a lesser extent in CBPE, but not in RPE. Thus, CD86 emerged as a candidate molecule in the suppression of T cell activation achieved by contact exposure to IPE.

Bottom Line: 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.Thus, ocular immune privilege is achieved in part by subversion of molecules that are usually used for conventional immune costimulation.

View Article: PubMed Central - PubMed

Affiliation: Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus