April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Dexamethasone Fails to Induce IL-10 Secreting T-Regulatory Cells in Steroid Refractory Uveitis
Author Affiliations & Notes
  • Lauren P. Schewitz-Bowers
    School of Clinical Sciences, University of Bristol, Bristol, United Kingdom
  • Andrew D. Dick
    School of Clinical Sciences, University of Bristol, Bristol, United Kingdom
  • Richard W. Lee
    School of Clinical Sciences, University of Bristol, Bristol, United Kingdom
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4303. doi:
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      Lauren P. Schewitz-Bowers, Andrew D. Dick, Richard W. Lee; Dexamethasone Fails to Induce IL-10 Secreting T-Regulatory Cells in Steroid Refractory Uveitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4303.

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

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Abstract

Purpose: : Glucocorticoids (GCs) exert a range of effects on CD4+ T cells to curb the immune response. Chief among these are their anti-proliferative effects. However, dexamethasone (Dex; synthethic GC) also induces secretion of the immunosuppressive cytokine IL-10. We have already shown that GCs fail to suppress proliferation of a subset of CD4+ T cells from steroid refractory (SR) uveitis patients. Therefore, the purpose of this study was to compare the capacity of GCs to induce IL-10 in CD4+ T cells in steroid sensitive (SS) and SR patients.

Methods: : CD4+ T cells from SS and SR uveitis patients were isolated and cultured in the presence of IL-2 containing RPMI media (N=10). IL-10 secreting T-regulatory cells (Tregs) were induced by culturing CD4+ cells with anti CD3/CD28 microbeads and 1x10-6M Dex for 4 days. Post culture intra-cellular interleukin (IL)-10, IL-4, IL-9, IL-17 and IFN-gamma expression was then quantified by flow cytometry (LSRII, BD Biosciences). Furthermore, Dex induced IL-10 cells were isolated using capture antibodies (Miltenyi Biotech) and their suppression of CD4+CD25- effector cells was functionally assessed in a standard Treg assay.

Results: : CD4+ T cells from SR patients failed to up regulate IL-10 expression in the presence of Dex (3.0% IL-10 expression for SR vs 8.8% IL-10 expression for SS). Dex did not change IL-17 expression but IL-4 and IFN-gamma were reduced. IL-9 was detected in less than 1% of cells before and after culture. Dex induced IL-10 secreting cells exhibited functional suppression of CD4+CD25- cells (1Treg:15 effector cell ratio).

Conclusions: : Dex fails to induce functionally suppressive IL-10 secreting CD4+ T cells in SR uveitis patients. This is independent of the effects on expression of other cytokines, and in particular the proportion of Th17 cells was undiminished by Dex in both SR and SS individuals. Our data suggests that differential control of Dex induced Treg function is a key driver of the SR phenotype in uveitis patients.

Keywords: immunomodulation/immunoregulation • corticosteroids • cytokines/chemokines 
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