Human CD4+CD25+ thymocytes and peripheral T cells have immune suppressive activity in vitro

Abstract

CD4+CD25+ T cells in mice and rats are capable of transferring protection against organ-specific autoimmune disease and colitis and suppressing the proliferation of other T cells after polyclonal stimulation in vitro. Here we describe the existence in humans of CD4+CD25+ T cells with the same in vitro characteristics. CD4+CD8-CD25+ T cells are present in both the thymus and peripheral blood of humans (∼ 10% of CD4+CD8- T cells), proliferate poorly in response to mitogenic stimulation and suppress the proliferation of CD4+CD25- cells in co-culture. This suppression requires cell contact and can be overcome by the addition of exogenous IL-2. CD4+CD25+ cells from thymus and blood were poor producers of IL-2 and IFN-γ, and suppressed the levels of these cytokines produced by CD4+CD25- cells. However, CD4+CD25+ PBL produced higher levels of IL-4 and similar amounts of IL-10 as CD4+CD25- cells. Regulatory CD4+CD25+ T cells have an activated phenotype in the thymus with expression of CTLA-4 and CD122 (IL-2Rβ). The fact that CD4+CD25+ regulatory T cells are present with a similar frequency in the thymus of humans, rats and mice, suggests that the role of these cells in the maintenance of immunological tolerance is an evolutionarily conserved mechanism.