May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
GITR Ligand Is Expressed in the Eye and Inhibits CD4+ T Cell Proliferation
Author Affiliations & Notes
  • B.J. Kim
    Howard Hughes Medical Institute - National Institutes of Health Research Scholars Program, National Eye Institute, Bethesda, MD, United States
  • Z. Li
    National Eye Institute, National Institutes of Health, Bethesda, MD, United States
  • C. Chan
    National Eye Institute, National Institutes of Health, Bethesda, MD, United States
  • D. Shen
    National Eye Institute, National Institutes of Health, Bethesda, MD, United States
  • C. Egwuagu
    National Eye Institute, National Institutes of Health, Bethesda, MD, United States
  • C. Yu
    National Eye Institute, National Institutes of Health, Bethesda, MD, United States
  • C. Nagineni
    National Eye Institute, National Institutes of Health, Bethesda, MD, United States
  • R. Nussenblatt
    National Eye Institute, National Institutes of Health, Bethesda, MD, United States
  • Footnotes
    Commercial Relationships  B.J. Kim, None; Z. Li, None; C. Chan, None; D. Shen, None; C. Egwuagu, None; C. Yu, None; C. Nagineni, None; R. Nussenblatt, None.
  • Footnotes
    Support  B.J. Kim is funded by the Howard Hughes Medical Institute as an HHMI-NIH Research Scholar
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 736. doi:
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      B.J. Kim, Z. Li, C. Chan, D. Shen, C. Egwuagu, C. Yu, C. Nagineni, R. Nussenblatt; GITR Ligand Is Expressed in the Eye and Inhibits CD4+ T Cell Proliferation . Invest. Ophthalmol. Vis. Sci. 2003;44(13):736.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: In addition to GITR’s (glucocorticoid induced TNF related receptor) ability to affect the suppressor activity of mouse CD4+CD25+ regulatory T cells, GITR has been described as a negative regulator of T cell proliferation based on data from GITR -/- mice T cells. Data from our lab demonstrate that levels of cell surface GITR on human CD4+ cells correlate with the disease activity of noninfectious uveitis. The human GITR ligand (GITRL) gene is reported to be expressed by HUVEC (human umbilical vein endothelial cell) cells and several tissues, suggesting that the receptor – ligand interaction enables local modulation of the immune response. We examined the expression of the GITRL gene by ocular cells and the function of GITRL. Methods: Reverse transcriptase PCR was used to examine the expression of the GITRL gene by a human RPE cell line (ARPE19), a human Müller cell line, and normal human RPE that was microdissected from frozen sections. The two cell lines were examined in the presence and absence of inflammatory cytokines. A functional role for GITRL was investigated with a proliferation assay. In this assay, purified human CD4+ cells, with and without soluble recombinant human GITRL, were activated by anti-CD3 (OKT3) and anti-CD28. Results: Expression of the GITRL gene was detected in ARPE19 cells, Müller cells, and normal RPE. This expression was upregulated by inflammatory cytokines in ARPE19 cells. Preliminary data from proliferation assays indicated that GITRL can inhibit the proliferation of activated CD4+ cells by as much as 40%. Conclusions: The GITR – GITRL interaction may provide local regulation of ocular inflammation. After ocular inflammation begins, GITRL may be produced by RPE and Müller cells to inhibit the proliferation of activated CD4+ T cells that infiltrate the area. The expression of the GITRL gene by Müller cells is consistent with our previous publication that a surface protein on Müller cells inhibits T cell proliferation (Caspi, R.R. et al. Science. 1987; 237: 1029-1032). The synthesis of GITRL by ocular cells could enable immunosuppression that contributes to mechanisms of immune privilege such as ACAID and limits the vision threatening inflammation of uveitis.

Keywords: immunomodulation/immunoregulation • autoimmune disease • retinal pigment epithelium 
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