Foxp3 Expression Is Decreased in Peripheral Blood Regulatory T Lymphocytes From Patients With Uveitis

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 CD25^high and CD127^low.

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