Regulatory CD4 T cells: expression of IL-2R alpha chain, resistance to clonal deletion and IL-2 dependency.

We recently characterized a CD4+ T cell population expressing the IL-2R alpha chain (CD25), producing IL-10 and resisting clonal deletion induced by viral superantigen (vSAG) encoded by mouse mammary tumor virus [MMTV(SW)]. We now report that these apoptosis-resistant cells are generated in the thymus but not from the immature CD4+ CD8+ thymocytes. They migrate from the thymus and are found in the periphery from at least the 10th day of life, after which they expand with the same kinetics in normal and MMTV(SW)-infected mice. Their strong capacity for expansion in the periphery makes this population insensitive to thymectomy in adulthood. CD4+ CD25+ cells were totally dependent on exogenous IL-2 for growth in vitro and in vivo, and were missing in IL-2 knockout (KO) mice. The absence of this population and/or an inability to produce IL-10 may be the missing link between IL-2R alpha KO, IL-2 KO and IL-10 KO mice, which all die of inflammatory bowel disease.