Infect Immun. 2010 May 24. [Epub ahead of print]
CD4 T-Cell Suppression by Cells from Toxoplasma gondii-Infected Retinas is Mediated by PD-L1
Charles E, Joshi S, Ash JD, Fox BA, Farris AD, Bzik DJ, Lang ML, Blader IJ.
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756; Arthritis and Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104.
In the inflamed retina, CD4(+) T-cells can cause retinal damage when they are not properly regulated. Since tissue expression of MHC Class II and co-stimulatory molecules is a key mechanism to regulate effector T-cells, we tested the hypothesis that upregulation of these proteins in the retina contributes to the regulation of CD4 T-cells. Here, we report that in retinas infected with the protozoan parasite Toxoplasma gondii MHC Class II is upregulated on infiltrating leukocytes as well as resident retinal cells including photoreceptors. Flow cytometric analysis indicated that B7 costimulatory family members (CD80, CD86, ICOS-L, and PD-L2) were not expressed on the Class II(+) cells. In contrast, PD-L1 (also named B7-H1 or CD274) was expressed on the majority of both hematopoietic and resident retinal Class II-expressing cells. Retinal cells from Toxoplasma-infected animals were able to suppress T-cell activation in a PD-L1-dependent manner. Finally, we demonstrate that MHC Class II and PD-L1 expression was critically dependent on IFNgamma expression. These data suggests that retinal MHC Class II and PD-L1 expression is a novel mechanism for the retina to protect itself from CD4 T-cell-mediated immune damage in ocular toxoplasmosis and other types of retinal immune responses.
PMID: 20498261 [PubMed - as supplied by publisher]