The role of cytokines (and not only) in inducing and expanding T regulatory type 1 cells.

T regulatory (Tr) type 1 cells are one of the most studied of CD4+ Tr cell subsets. They are distinct from other T-cell subsets in their cytokine production profile and in their ability to suppress immune responses both in vitro and in vivo. Human and murine Tr1 cells share many properties, but signals regarding their in vitro induction are different. Although culture of murine naive CD4+ cells in the presence of high doses of interleukin (IL)-10 is sufficient for Tr1 induction, human naive CD4+ T cells can give rise to Tr1 cells when cultured with IL-10 and interferon-alpha. Tr1 cells can also be induced in vivo, although the mere administration of IL-10 is not sufficient to generate Tr1 cells in a context of murine allogenic transplant. IL-10 needs to be combined with immunosuppressive compounds, which are permissive for tolerance induction, to generate or expand Tr1 cells in vivo and mediate antigen-specific tolerance. Whether this combined treatment can also be used in humans is still an open question.