CD4 T-cell suppression by cells from Toxoplasma gondii-infected retinas is mediated by surface protein PD-L1.
In the inflamed retina, CD4(+) T cells can cause retinal damage when they are not properly regulated. Since tissue expression of major histocompatibility complex (MHC) class II and costimulatory molecules is a key mechanism for regulating 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 on resident retinal cells, including photoreceptors. Flow cytometric analysis indicated that B7 costimulatory family members (CD80, CD86, ICOS-L, and programmed death ligand 2 [PD-L2]) were not expressed on class II(+) cells. In contrast, PD-L1 (also named B7-H1 or CD274) was expressed on the majority of both hematopoietic and resident retinal MHC 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 the expression of MHC class II and PD-L1 was critically dependent on gamma interferon (IFN-gamma) expression. These data suggest that retinal MHC class II and PD-L1 expression is a novel mechanism by which the retina protects itself from CD4 T-cell-mediated immune damage in ocular toxoplasmosis and other types of retinal immune responses.
Charles
Elizabeth
E
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd., Oklahoma City, OK 73104, USA.
Joshi
Sunil
S
Ash
John D
JD
Fox
Barbara A
BA
Farris
A Darise
AD
Bzik
David J
DJ
Lang
Mark L
ML
Blader
Ira J
IJ
D000818:Animals; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance; D007962:Leukocytes / Q000276:immunology; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides; D020419:Photoreceptor Cells, Vertebrate / Q000276:immunology; D012160:Retina / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*
D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D010455:Peptides