Retinal pericytes inhibit activated T cell proliferation

Invest Ophthalmol Vis Sci. 2011 Nov 21;52(12):9005-10. doi: 10.1167/iovs.11-8008.

Abstract

Purpose: To test the hypothesis that retinal pericytes (RPCs) are immunosuppressive; therefore, their loss of function under hyperglycemic conditions favors retinal inflammation and contributes to the pathogenesis of diabetic retinopathy (DR).

Methods: Isolated mouse and human RPCs were tested in T cell function assays to evaluate their capability of inhibiting T cell responses. To elucidate the underlying mechanisms, transwell systems, blocking mAbs against PD-L1 and IL-10 were used. The efficacy of RPCs in protecting retinal endothelial cells (RECs) from inflammation-induced apoptosis was assessed by apoptosis detection staining. Finally, to test whether hyperglycemic conditions impair the immunomodulatory activity of RPCs, RPCs pre-incubated in high glucose or methylglyoxal (MGO) were evaluated using the T cell proliferation assays.

Results: RPCs profoundly inhibited activated T cell proliferation and inflammatory cytokine production. The T cell inhibitory activity of RPCs was decreased, but was not abolished, in transwell experiments. RPCs express PD-L1, and blocking PD-L1 reduced RPCs' efficacy of T cell inhibition. RPCs also produce IL-10, and neutralization of IL-10 reduced their immunosuppressive activity. There were significantly reduced numbers of inflammation-induced apoptosis-detected RECs in the presence of RPCs. Incubation of RPCs with either high glucose or MGO reduced the activity of RPCs to inhibit activated T cell proliferation.

Conclusions: RPCs are highly immunosuppressive and they protected RECs from inflammation-mediated apoptosis. Hyperglycemic conditions impaired the T cell inhibitory activity of RPCs. These results reveal a new function of RPCs, and its regulation under hyperglycemic conditions. This may represent a novel mechanism by which RPCs contribute to preservation of retinal integrity in diseases, including DR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Cell Communication / immunology*
  • Cell Division / immunology
  • Cell Line, Transformed
  • Diabetic Retinopathy / immunology
  • Diabetic Retinopathy / pathology
  • Endothelial Cells / cytology*
  • Endothelial Cells / immunology
  • Humans
  • Hyperglycemia / immunology
  • Hyperglycemia / pathology
  • Membrane Proteins / immunology
  • Mice
  • Mice, Transgenic
  • Pericytes / cytology*
  • Pericytes / immunology
  • Retina / cytology*
  • Retina / immunology
  • Retinitis / immunology*
  • Retinitis / pathology
  • T-Lymphocytes / cytology*

Substances

  • Membrane Proteins