Abstract
CD25(+)CD4(+) regulatory T cells suppress T cell activation and regulate multiple immune reactions in in vitro and in vivo studies. To define the regulatory function of human CD25(+)CD4(+) T cells at various stages of maturity, we investigated in detail the functional differences of CD25(+)CD4(+) T cells from thymocytes, cord blood (CB), and adult peripheral blood (APB). CB CD25(+)CD4(+) T cells displayed low-FOXP3 protein expression level and had no suppressive activity. In contrast, CD25(+)CD4(+) T cells from thymocytes or APB expressed high expression level of FOXP3 protein associated with significant suppressive activity. Although CB CD25(+)CD4(+) T cells exhibited no suppressive activity, striking suppressive activity was observed following expansion in culture associated with increased FOXP3 expression and a shift from the CD45RA(+) to the CD45RA(-) phenotype. These functional differences in CD25(+)CD4(+) T cells from Thy, CB, and APB hence suggest a pathway of maturation for Treg in the peripheral immune system.