April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Retinal Neurons Express MHC Class II and PD-L1 to Suppress Activated T cells in Toxoplasma gondii-Infected Eyes
Author Affiliations & Notes
  • Kevin M. Brown
    Microbiology & Immunology,
    Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • Elizabeth Charles
    Microbiology & Immunology,
    Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • Sunil Joshi
    Microbiology & Immunology,
    Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • David M. Sherry
    Cell Biology,
    Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • Muayyad R. Al-Ubaidi
    Cell Biology,
    Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • Mark Lang
    Microbiology & Immunology,
    Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • Ira Blader
    Microbiology & Immunology,
    Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • Footnotes
    Commercial Relationships  Kevin M. Brown, None; Elizabeth Charles, None; Sunil Joshi, None; David M. Sherry, None; Muayyad R. Al-Ubaidi, None; Mark Lang, None; Ira Blader, None
  • Footnotes
    Support  Oklahoma Center for the Advancement of Science and Technology Grant HR05-138S and NIH Grant A069986 to I.B.
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3390. doi:
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      Kevin M. Brown, Elizabeth Charles, Sunil Joshi, David M. Sherry, Muayyad R. Al-Ubaidi, Mark Lang, Ira Blader; Retinal Neurons Express MHC Class II and PD-L1 to Suppress Activated T cells in Toxoplasma gondii-Infected Eyes. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3390.

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Abstract

Purpose: : The retina is an immune-privileged tissue that suppresses immune surveillance and activation. Upon infection by pathogens, the immune-privileged state of the retina must be suppressed or overcome to control the infection. Our lab has used infections with the retinal parasite Toxoplasma gondii as a model for immune privilege regulation. Because retinal damage in Toxoplasma-infected eyes is due to dysregulated CD4+ T cells, the goal of this study was to determine how intraretinal CD4+ T cells are regulated.

Methods: : To study acute infection, mice were intravitreally-injected with Toxoplasma parasites or vehicle alone. Eyes were enucleated 6 days post-injection and subjected to flow cytometric, immunohistochemical, and functional analyses. To study chronic infections, WT or PD-L1-/- mice were infected intraperitoneally with Toxoplasma parasites. Eyes were enucleated 30 days post-infection and analyzed by flow cytometry and histochemistry. Neuroretinal immunoregulatory function was assessed in vitro using the murine cone photoreceptor cell line 661W.

Results: : Acute Toxoplasma infection leads to MHC class II expression on infiltrating leukocytes as well as most types of retinal neurons. Nearly all MHC class II+ cells expressed the co-inhibitory molecule programmed death-ligand 1 (PD-L1), but not positively acting co-stimulatory molecules CD80, CD86, or ICOS-L. Total retinal cells from Toxoplasma-infected mouse eyes were able to suppress T cell activation in a PD-L1-dependent manner. Functionally, loss of PD-L1 resulted in increased retinal pathology and T cell infiltration compared to WT control mice. IFNγ was critical for the induction of both MHC class II and PD-L1. Finally, IFNγ-primed 661W photoreceptors expressed MCH class II and PD-L1 and were able to robustly inhibit CD4+ T cell activation.

Conclusions: : The upregulation of MHC class II and PD-L1 in Toxoplasma-infected retinas appears be to be an important mechanism regulating CD4+ T cell infiltrates. Based on these data, we propose a novel function for retinal neurons - inducible regulators of retinal immune privilege.

Keywords: immune tolerance/privilege • retinitis • microbial pathogenesis: experimental studies 
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