Suppressor effector function of CD4(+)CD25(+) immunoregulatory T cells is antigen nonspecific

CD4(+)CD25(+) T cells represent a unique population of professional suppressor T cells that prevent induction of organ-specific autoimmune disease. In vitro, CD4(+)CD25(+) cells were anergic to simulation via the TCR and when cultured with CD4(+)CD25(-) cells, markedly suppressed polyclonal T cell proliferation by specifically inhibiting the production of IL-2, Suppression was cytokine independent, cell contact dependent, and required activation of the suppressors via their TCR, Further characterization of the CD4(+)CD25(+) population demonstrated that they do not contain memory or activated T cells and that they act through an APC-independent mechanism. CD4(+)CD25(+) T cells isolated from TCR transgenic (Tg) mice inhibited responses of CD4(+)CD25(-) Tg T cells to the same Ag, but also inhibited the Ag-specific responses of Tg cells specific for a distinct Ag, Suppression required that both peptide/MHC complexes be present in the same culture, but the Ags could be presented by two distinct populations of APC,When CD4(+)CD25(+) T cells were cultured with anti-CD3 and IL-2, they expanded, remained anergic, and in the absence of restimulation via their TCR, suppressed Ag-specific responses of CD4(+)CD25(-) T cells from multiple TCR transgenics, Collectively, these data demonstrate that CD4(+)CD25(+) T cells require activation via their TCR to become suppressive, but once activated, their suppressor effector function is completely nonspecific, The cell surface molecules involved in this T-T interaction remain to be characterized.