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Diminished frequency and function of CD4+CD25high regulatory T cells associated with active uveitis in Vogt-Koyanagi-Harada syndrome.
Invest Ophthalmol Vis Sci. 2008 Aug; 49(8):3475-82.IO

Abstract

PURPOSE

CD4(+)CD25(high) regulatory T (Treg) cells have been shown to be involved in the pathogenesis of autoimmune diseases. Vogt-Koyanagi-Harada (VKH) syndrome is an organ-specific autoimmune disease. This study was designed to phenotypically and functionally characterize peripheral blood CD4(+)CD25(high) Treg cells in VKH patients with active uveitis.

METHODS

Blood samples were taken from 30 patients with active VKH, 19 patients with inactive VKH, and 26 healthy controls. Peripheral blood mononuclear cells were subjected to flow cytometry for analysis of phenotypes of the CD4(+)CD25(high) Treg cells. For functional analysis, CD4(+)CD25(high) Treg cells and CD4(+)CD25(-) T cells were separated by means of magnetic-assisted cell sorting and subsequently cocultured for 6 days. The proliferation of CD4(+)CD25(-) T cells was measured by [(3)H] thymidine incorporation assay. The levels of IFN-gamma, IL-17, and IL-13 in the supernatants were determined by enzyme-linked immunosorbent assay.

RESULTS

Significantly decreased frequencies of CD4(+)CD25(high) Treg cells and percentages of FOXP3(+) cells in these Treg cells were shown in patients with active VKH. Treg cells from patients with active VKH showed a significant deficiency in suppressing the proliferation of CD4(+)CD25(-) T cells and inhibiting the production of IFN-gamma and IL-13 by CD4(+)CD25(-) T cells. CD4(+)CD25(high) Treg cells from VKH patients or healthy controls did not markedly inhibit or promote IL-17 production.

CONCLUSIONS

A significantly decreased frequency and diminished function of CD4(+)CD25(high) Treg cells is associated with active uveitis in patients with VKH syndrome. These results suggest that these dysfunctional CD4(+)CD25(high) Treg cells may play a role in the pathogenesis of uveitis in VKH syndrome.

Authors+Show Affiliations

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Uveitis Study Center of Sun Yat-sen University, Guangzhou, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18421089

Citation

Chen, Lina, et al. "Diminished Frequency and Function of CD4+CD25high Regulatory T Cells Associated With Active Uveitis in Vogt-Koyanagi-Harada Syndrome." Investigative Ophthalmology & Visual Science, vol. 49, no. 8, 2008, pp. 3475-82.
Chen L, Yang P, Zhou H, et al. Diminished frequency and function of CD4+CD25high regulatory T cells associated with active uveitis in Vogt-Koyanagi-Harada syndrome. Invest Ophthalmol Vis Sci. 2008;49(8):3475-82.
Chen, L., Yang, P., Zhou, H., He, H., Ren, X., Chi, W., Wang, L., & Kijlstra, A. (2008). Diminished frequency and function of CD4+CD25high regulatory T cells associated with active uveitis in Vogt-Koyanagi-Harada syndrome. Investigative Ophthalmology & Visual Science, 49(8), 3475-82. https://doi.org/10.1167/iovs.08-1793
Chen L, et al. Diminished Frequency and Function of CD4+CD25high Regulatory T Cells Associated With Active Uveitis in Vogt-Koyanagi-Harada Syndrome. Invest Ophthalmol Vis Sci. 2008;49(8):3475-82. PubMed PMID: 18421089.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diminished frequency and function of CD4+CD25high regulatory T cells associated with active uveitis in Vogt-Koyanagi-Harada syndrome. AU - Chen,Lina, AU - Yang,Peizeng, AU - Zhou,Hongyan, AU - He,Hao, AU - Ren,Xiangrong, AU - Chi,Wei, AU - Wang,Li, AU - Kijlstra,Aize, Y1 - 2008/04/17/ PY - 2008/4/19/pubmed PY - 2008/8/13/medline PY - 2008/4/19/entrez SP - 3475 EP - 82 JF - Investigative ophthalmology & visual science JO - Invest. Ophthalmol. Vis. Sci. VL - 49 IS - 8 N2 - PURPOSE: CD4(+)CD25(high) regulatory T (Treg) cells have been shown to be involved in the pathogenesis of autoimmune diseases. Vogt-Koyanagi-Harada (VKH) syndrome is an organ-specific autoimmune disease. This study was designed to phenotypically and functionally characterize peripheral blood CD4(+)CD25(high) Treg cells in VKH patients with active uveitis. METHODS: Blood samples were taken from 30 patients with active VKH, 19 patients with inactive VKH, and 26 healthy controls. Peripheral blood mononuclear cells were subjected to flow cytometry for analysis of phenotypes of the CD4(+)CD25(high) Treg cells. For functional analysis, CD4(+)CD25(high) Treg cells and CD4(+)CD25(-) T cells were separated by means of magnetic-assisted cell sorting and subsequently cocultured for 6 days. The proliferation of CD4(+)CD25(-) T cells was measured by [(3)H] thymidine incorporation assay. The levels of IFN-gamma, IL-17, and IL-13 in the supernatants were determined by enzyme-linked immunosorbent assay. RESULTS: Significantly decreased frequencies of CD4(+)CD25(high) Treg cells and percentages of FOXP3(+) cells in these Treg cells were shown in patients with active VKH. Treg cells from patients with active VKH showed a significant deficiency in suppressing the proliferation of CD4(+)CD25(-) T cells and inhibiting the production of IFN-gamma and IL-13 by CD4(+)CD25(-) T cells. CD4(+)CD25(high) Treg cells from VKH patients or healthy controls did not markedly inhibit or promote IL-17 production. CONCLUSIONS: A significantly decreased frequency and diminished function of CD4(+)CD25(high) Treg cells is associated with active uveitis in patients with VKH syndrome. These results suggest that these dysfunctional CD4(+)CD25(high) Treg cells may play a role in the pathogenesis of uveitis in VKH syndrome. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/18421089/Diminished_frequency_and_function_of_CD4+CD25high_regulatory_T_cells_associated_with_active_uveitis_in_Vogt_Koyanagi_Harada_syndrome_ L2 - http://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.08-1793 DB - PRIME DP - Unbound Medicine ER -