Kottoor, Sherine Hermangild (2011)
Ph.D. thesis, University of Birmingham.
Regulatory T cells (Treg) are critical for the maintenance of tolerance to self and control of inflammation. Defects in Treg have been reported for a number of autoimmune and inflammatory diseases. In this thesis I wished to determine whether there are quantitative and/ or qualitative defects of Treg in patients with idiopathic non-infectious uveitis.
Using stringent gating procedures, an increased frequency of CD4+CD25highCD127low Treg was observed in the peripheral blood of acute anterior uveitis (AAU) patients but not those with chronic disease. Treg from both acute and chronic anterior uveitis patients expressed defective suppressive capacity in vitro.
I also observed an accumulation of memory Treg in the aqueous humor from AAU patients, expressing high levels of FoxP3 and CTLA-4. In vitro activated Treg upregulated their FoxP3 expression to levels as seen in the eye, suggesting that the aqueous humor Treg might be recently activated. Using an in vitro model for analysing Treg function, I observed that exposure to uveitis aqueous humor did not affect the suppressive ability of Treg.
In summary, Treg with a potent regulatory phenotype accumulate in the aqueous humor of acute anterior uveitis patients, whereas the peripheral Treg population from both chronic and acute patients express a defective function.
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