Abstract
CD4(+) CD25(+) regulatory T cells prevent organ-specific autoimmune diseases in various animal models. We analysed human lymphoid tissues to identify similar CD25(+) regulatory T cells. Adult peripheral blood contained two populations of CD4(+) T cells that expressed CD25 at different densities. The larger population (approximately 40%) expressed intermediate levels of CD25 (CD25(+)) and displayed a memory T-cell phenotype (CD45RA-/RO(+), CD45RB(low), CD95(+), CD62L(low), CD38(low)). The smaller population of cells (approximately 2%) expressed very high levels of CD25 (CD25(++)). In addition to the activation/memory T-cell antigens mentioned above they also expressed intracellular CD152 (CTLA-4) as well as enhanced levels of cell-surface CD122, similar to the murine CD4(+) CD25(+) regulatory counterpart. To exclude that the CD25(++) cells had not been recently primed by external antigen we analysed cord blood and thymus. CD25(++), CD152(+) and CD122(++) cells were present in paediatric thymus (10% of CD4(+) CD8(-) thymocytes) expressing signs of recent selection (CD69+) and in cord blood (5% of CD4(+) cells) where they showed a naive phenotype. In addition, cord blood contained a small population of CD25(+) cells (approximately 2% of CD4 T cells) that were CD152(-) and CD122(low) and displayed signs of activation. Together with published data that CD25(+) CD25(++) cells from the thymus and peripheral blood are regulatory, our results suggest that regulatory CD25(+) T cells leave the thymus in a naïve state and become activated in the periphery.