May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Foxp3 Expression Is Decreased in Peripheral Blood Regulatory T Lymphocytes From Patients With Uveitis
Author Affiliations & Notes
  • S. J. Curnow
    Division of Immunity & Infection, University of Birmingham, Birmingham, United Kingdom
    Institute of Biomedical Research,
    Academic Unit of Ophthalmology,
  • S. Kottoor
    Division of Immunity & Infection, University of Birmingham, Birmingham, United Kingdom
    Institute of Biomedical Research,
    Academic Unit of Ophthalmology,
  • K. Morsley
    Division of Immunity & Infection, University of Birmingham, Birmingham, United Kingdom
    Institute of Biomedical Research,
    Academic Unit of Ophthalmology,
  • R. Khanfer
    Division of Immunity & Infection, University of Birmingham, Birmingham, United Kingdom
    Institute of Biomedical Research,
    Academic Unit of Ophthalmology,
  • A. K. O. Denniston
    Division of Immunity & Infection, University of Birmingham, Birmingham, United Kingdom
    Institute of Biomedical Research,
    Academic Unit of Ophthalmology,
  • P. J. Tomlins
    Division of Immunity & Infection, University of Birmingham, Birmingham, United Kingdom
    Academic Unit of Ophthalmology,
  • S. Rauz
    Division of Immunity & Infection, University of Birmingham, Birmingham, United Kingdom
    Institute of Biomedical Research,
    Academic Unit of Ophthalmology,
  • M. Salmon
    Division of Immunity & Infection, University of Birmingham, Birmingham, United Kingdom
    Institute of Biomedical Research,
  • K. P. Piper
    Institute of Cancer Studies, University of Birmingham, Birmingham, United Kingdom
  • P. I. Murray
    Division of Immunity & Infection, University of Birmingham, Birmingham, United Kingdom
    Academic Unit of Ophthalmology,
  • Footnotes
    Commercial Relationships  S.J. Curnow, None; S. Kottoor, None; K. Morsley, None; R. Khanfer, None; A.K.O. Denniston, None; P.J. Tomlins, None; S. Rauz, None; M. Salmon, None; K.P. Piper, None; P.I. Murray, None.
  • Footnotes
    Support  EU FP6 Marie Curie Actions and Medical Research Council UK (G0600416)
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3233. doi:
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      S. J. Curnow, S. Kottoor, K. Morsley, R. Khanfer, A. K. O. Denniston, P. J. Tomlins, S. Rauz, M. Salmon, K. P. Piper, P. I. Murray; Foxp3 Expression Is Decreased in Peripheral Blood Regulatory T Lymphocytes From Patients With Uveitis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3233.

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Abstract

Purpose: : Naturally occurring regulatory T cells (nTreg) expressing the transcription factor FoxP3 are known to be critical for the maintenance of self-tolerance, controlling both innate and adaptive immune responses. In experimental animal models nTreg have been shown to inhibit intraocular inflammation (uveitis). We wished to determine whether there are alterations in the number or phenotype of nTreg in patients with uveitis.

Methods: : Peripheral blood mononuclear cells were isolated from healthy controls and patients with acute anterior and pan uveitis, both untreated and treated with topical glucocorticoids. Multi-colour flow cytometry was performed on these cells using antibodies specific for CD4, CD45RO, CD69, FoxP3, CD127 (IL-7Rα) and CD25 (IL-2Rα). nTreg were defined as those CD4+ lymphocytes that are CD25high and CD127low.

Results: : The frequency of peripheral blood nTreg was not significantly altered between controls and any group of uveitis patients. However, the nTreg FoxP3 expression level was significantly decreased in patients with uveitis. Decreased FoxP3 expression was evident in both CD45RA+ (naive) and CD45RO+ (primed) nTreg. The activation marker CD69 was not expressed on any of these cells, indicating that the FoxP3 expression was not due to recent activation.

Conclusions: : Peripheral blood nTreg in patients with uveitis are present in normal numbers but have a reduced expression of FoxP3. We are currently investigating if this low level expression results in a functional deficit.

Keywords: immunomodulation/immunoregulation • uveitis-clinical/animal model 
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