PReS-FINAL-1002: Dissecting the dissociation of foxp3 and cd25 expression on cd4+ t cells in synovial fluid identifies three distinct subpopulations of human t regulatory cells present at the chronically inflamed site

Introduction T regulatory cells (Treg), vital to prevent autoimmunity, are defined by expression of FoxP3 in combination with high CD25 and low CD127 expression. It has been reported, however, that upon in vitro activation, conventional T cells (Tconv) can manifest phenotypic marks associated with Treg and, as such, expression of these markers alone is insufficient to determine Treg commitment. A unique feature of Treg is the presence of a Treg specific demethylated region (TSDR) in intron 1 of the FOXP3 gene. This distinguishes activated Tconv from bona fide Treg. In CD4 T cells from the joints of children with JIA we have observed a clear dissociation of CD25 and FoxP3 expression. The relationship between CD25, CD127 and FoxP3 expression and commitment to Treg lineage at the inflamed site is unclear; meaningful investigation is hampered by the technical difficulties in isolating cells based on FoxP3 status.