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