GARP as a Tool to Identify Antigen-Specific Human Tregs.

Abstract

Naturally occurring regulatory T cells (nTregs) are key to immunological tolerance, thereby preventing autoimmunity, but are equally considered to impact desirable immune responses such as clearance of infections or eradication of tumours. Due to technical limitations, however, only few studies addressed directly if Tregs specific for non-self proteins such as recall antigens do exist in man. We employed GARP (Glycoprotein-A Repetitions Predominant), a recently described receptor for latent Transforming Growth Factor beta, as a marker to label activated Tregs after stimulation with various infectious disease antigens. Interestingly, in most donors mounting an antigen-specific T effector cell response, GARP was induced on a population of cells that resembled memory Tregs, being FoxP3+CD25highCTLA-4highCD45RA-. Furthermore, activated GARP+ T cells showed other hallmarks of nTregs such as demethylation of the TSDR locus, accompanied by a lack of cytokine production. Our data indicate that GARP can be used as a novel tool to directly monitor and isolate nTregs in the context of infection; studies are ongoing to track those cells in chronic infectious diseases such as Hepatitis C and in transplant patients suffering from recurring opportunistic infections.