T-regulatory 1 cells: A novel subset of CD4(+)T cells with immunoregulatory properties

Clonal deletion and clonal anergy are well established mechanisms of periph eral tolerance. A role has also been described for clonal suppression by re gulatory cells in the induction of peripheral tolerance to a variety of ant igens, However, it has been difficult to isolate regulatory cells and to de fine their mechanism of action. We have recently reported the in vitro gene ration and characterization of a novel subset of CD4(+) T cells that have r egulatory properties and are able to suppress antigen-specific immune respo nses in vitro and in vivo. These T-regulatory 1 (Tr1) cells are defined by their unique profile of cytokine production and make high levels of IL-10 a nd TGF-beta, but no IL-4 or IL-2, The IL-10 and TGF-beta produced by these cells mediate the inhibition of primary naive T cells in vitro. There is al so evidence that Tr1 cells exist in vivo, and we have documented the presen ce of high IL-10-producing CD4(+) T cells in patients with severe combined immunodeficiency who have received allogeneic stem-cell transplants, These findings support the notion that Tr1 cells are involved in the regulation o f peripheral tolerance and that they could potentially be used as a cellula r therapy to modulate immune responses in vivo.