CD4 T-cell suppression by cells from Toxoplasma gondii-infected retinas is mediated by surface protein PD-l1

Elizabeth Charles, Sunil Joshi, John D. Ash, Barbara A. Fox, A. Darise Farris, David J. Bzik, Mark L. Lang, Ira J. Blader

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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-γ) 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.

Original languageEnglish (US)
Pages (from-to)3484-3492
Number of pages9
JournalInfection and Immunity
Volume78
Issue number8
DOIs
StatePublished - Aug 1 2010
Externally publishedYes

Fingerprint

Toxoplasma
Major Histocompatibility Complex
Retina
Membrane Proteins
T-Lymphocytes
Ocular Toxoplasmosis
Vertebrate Photoreceptor Cells
Interferon-gamma
Parasites
Leukocytes
Up-Regulation
Ligands
Proteins

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

CD4 T-cell suppression by cells from Toxoplasma gondii-infected retinas is mediated by surface protein PD-l1. / Charles, Elizabeth; Joshi, Sunil; Ash, John D.; Fox, Barbara A.; Farris, A. Darise; Bzik, David J.; Lang, Mark L.; Blader, Ira J.

In: Infection and Immunity, Vol. 78, No. 8, 01.08.2010, p. 3484-3492.

Research output: Contribution to journalArticle

Charles, Elizabeth ; Joshi, Sunil ; Ash, John D. ; Fox, Barbara A. ; Farris, A. Darise ; Bzik, David J. ; Lang, Mark L. ; Blader, Ira J. / CD4 T-cell suppression by cells from Toxoplasma gondii-infected retinas is mediated by surface protein PD-l1. In: Infection and Immunity. 2010 ; Vol. 78, No. 8. pp. 3484-3492.
@article{d610d87a9c194c96b86d516bb0834180,
title = "CD4 T-cell suppression by cells from Toxoplasma gondii-infected retinas is mediated by surface protein PD-l1",
abstract = "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-γ) 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.",
author = "Elizabeth Charles and Sunil Joshi and Ash, {John D.} and Fox, {Barbara A.} and Farris, {A. Darise} and Bzik, {David J.} and Lang, {Mark L.} and Blader, {Ira J.}",
year = "2010",
month = "8",
day = "1",
doi = "10.1128/IAI.00117-10",
language = "English (US)",
volume = "78",
pages = "3484--3492",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "8",

}

TY - JOUR

T1 - CD4 T-cell suppression by cells from Toxoplasma gondii-infected retinas is mediated by surface protein PD-l1

AU - Charles, Elizabeth

AU - Joshi, Sunil

AU - Ash, John D.

AU - Fox, Barbara A.

AU - Farris, A. Darise

AU - Bzik, David J.

AU - Lang, Mark L.

AU - Blader, Ira J.

PY - 2010/8/1

Y1 - 2010/8/1

N2 - 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-γ) 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.

AB - 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-γ) 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.

UR - http://www.scopus.com/inward/record.url?scp=77955298874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955298874&partnerID=8YFLogxK

U2 - 10.1128/IAI.00117-10

DO - 10.1128/IAI.00117-10

M3 - Article

C2 - 20498261

AN - SCOPUS:77955298874

VL - 78

SP - 3484

EP - 3492

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 8

ER -