Retinal pericytes inhibit activated T cell proliferation

Zhidan Tu, Yan Li, Dawn S. Smith, Nader Sheibani, Suber Huang, Timothy Kern, Feng Lin

Research output: Contribution to journalArticle

48 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9005-9010
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number12
DOIs
StatePublished - Nov 2011

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Tu, Z., Li, Y., Smith, D. S., Sheibani, N., Huang, S., Kern, T., & Lin, F. (2011). Retinal pericytes inhibit activated T cell proliferation. Investigative Ophthalmology and Visual Science, 52(12), 9005-9010. https://doi.org/10.1167/iovs.11-8008