Cutting edge:: Size and diversity of CD4+ CD25high Foxp3+ regulatory T cell repertoire in humans:: evidence for similarities and partial overlapping with CD4+ CD25-T cells

Both differentiation and function of CD4+ CD25(high) naturally arising regulatory T cells (Treg), which play a key role in the control of autoimmunity, are thought to depend on TCR specificity. In the present study, we comparatively measured the alpha beta TCR repertoire sizes of human peripheral blood Treg and CD4(+) CD25(-) T cells by using a methodology based on PCR amplification and sequencing analysis. We show that Treg use a large unrestricted alpha beta TCR repertoire, the size and diversity of which are closely similar to those of CD4(+) CD25(-) Tcells, with a mean estimated size of 3.5 x 10(6) distinct alpha beta TCR vs 4.7 x 10(6) distinct alpha beta TCRfor CD4(+) CD25(-) T cells. In addition, a 24% overlap between the repertoires of these two CD4+ subsets in the peripbery is found. These data emphasize the intersection between naturally occurring Treg and effector T cell peripheral repertoires and provide new insights into the ontogeny of Treg in humans.