July 2018
Volume 59, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2018
Clinical Remission of Sight-threatening Uveitits is Characterised by an Upregulation of Peripheral TIGIT+ Treg and an Increased Ratio of T reg to T-bet+ T cells
Author Affiliations & Notes
  • Rachel J Healy
    Ophthalmology, Musgrove Park Hospital, Cheltenham, United Kingdom
  • Elewys Gemma Hearne
    Royal United Hospital , Bath, United Kingdom
  • Rose Gilbert
    University College London, London, United Kingdom
    Moorfields Eye Hospital, London, United Kingdom
  • Xiaozhe Zhang
    University College London, London, United Kingdom
    Moorfields Eye Hospital, London, United Kingdom
  • Oren Tomkins-Netzer
    University College London, London, United Kingdom
    Moorfields Eye Hospital, London, United Kingdom
  • Michael Ehrenstein
    University College London, London, United Kingdom
  • Virginia Calder
    University College London, London, United Kingdom
  • Susan Lightman
    University College London, London, United Kingdom
    Moorfields Eye Hospital, London, United Kingdom
  • Footnotes
    Commercial Relationships   Rachel Healy, None; Elewys Hearne, None; Rose Gilbert, None; Xiaozhe Zhang, None; Oren Tomkins-Netzer, None; Michael Ehrenstein, None; Virginia Calder, None; Susan Lightman, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2520. doi:https://doi.org/
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      Rachel J Healy, Elewys Gemma Hearne, Rose Gilbert, Xiaozhe Zhang, Oren Tomkins-Netzer, Michael Ehrenstein, Virginia Calder, Susan Lightman; Clinical Remission of Sight-threatening Uveitits is Characterised by an Upregulation of Peripheral TIGIT+ Treg and an Increased Ratio of T reg to T-bet+ T cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2520. doi: https://doi.org/.

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

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Abstract

Purpose : Non-infectious uveitis is mediated by pro-inflammatory Th1 and Th17 T-cell subsets and naturally-occurring immunosuppressive CD4+CD25+FoxP3+ T-regulatory cells (Treg). Treg may be involved in resolution of inflammation and in the maintenance of clinical remission. The aim of this study was to investigate whether there is a peripheral blood immunoregulatory phenotype associated with clinical remission of sight-threatening uveitis.

Methods : The study included patients active uveitic disease, control subjects and patients, with previously active disease, in clinical remission induced by immunosuppressive drugs. Isolated PBMC from peripheral blood samples from prospectively recruited subjects were analysed by flow cytometry for CD3, CD4, CD8, FoxP3, TIGIT, T-bet and RORγ-t. DNA methylation levels of FOXP3 TSDR, FOXP3 Promoter, TBX21, RORC2 and TIGIT loci were determined in cryopreserved PBMC using an NGS sequencing approach. Related cytokines were measured in blood sera. Functional suppressive capacity of Treg was assessed using T-cell proliferation assays.

Results : Fifty patients with non-anterior uveitis and 10 control subjects were recruited. The frequency of CD4+CD25+FoxP3+ Treg, TIGIT+ Treg, and the ratio of Treg to Th1 was significantly higher in remission patients compared to patients with active uveitic disease. Treg from patients in clinical remission demonstrated a high level of in vitro suppressive function compared to Treg from control subjects and Treg from patients with untreated active disease. PBMC from patients in clinical remission had significantly lower methylation levels at the FOXP3 TSDR, FOXP3 promoter and TIGIT loci and higher levels at RORC loci than those with active disease. Clinical remission was also associated with significantly higher serum levels of TGF-β and IL-10, which positively correlated with Treg levels, and lower serum levels of IFNγ, IL-17A and IL-22 compared to patients with active disease.

Conclusions : Clinical remission of sight-threatening uveitis has an immunoregulatory phenotype, characterized by upregulation of peripheral TIGIT+ Treg and an increased ratio of Treg to T-bet+ T-cells. These findings may assist with individualized therapy of uveitis, by informing whether drug therapy has induced phenotypically stable Treg and long-term clinical remission.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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