T-regulatory 1 cells: a novel subset of CD4 T cells with immunoregulatory properties.
Clonal deletion and clonal anergy are well established mechanisms of peripheral tolerance. A role has also been described for clonal suppression by regulatory cells in the induction of peripheral tolerance to a variety of antigens. However, it has been difficult to isolate regulatory cells and to define their mechanism of action. We have recently reported the in vitro generation and characterization of a novel subset of CD4(+) T cells that have regulatory properties and are able to suppress antigen-specific immune responses 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 and 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 also evidence that Tr1 cells exist in vivo, and we have documented the presence 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 of peripheral tolerance and that they could potentially be used as a cellular therapy to modulate immune responses in vivo.
Levings
M K
MK
Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
Roncarolo
M G
MG
D000917:Antibody Formation / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000145:classification* / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D016207:Cytokines; D016212:Transforming Growth Factor beta; D016753:Interleukin-10