Human Type 1 T Regulatory Cells

Abstract

IL-10 producing T regulatory type 1 (Tr1) cells were first identified in 1994 in severe combined immunodeficient patients successfully transplanted with allogeneic hemtaopoietic stem cells. Interestingly, the presence of Tr1 cells in vivo correlated with long term allograft tolerance without the need of immunosuppressive treatment. Since then, Tr1 cells were further characterized and efficient ways for their in vitro generation were developed. It is now evident that Tr1 cells represent a unique T cell subset, distinct from Th1, Th2, and Th17 cells and also from other T regulatory cells. Tr1 cells arise from naive precursors and are characterized by the production of high levels of IL-10 in the absence of IL-4. They are anergic cells which suppress proliferation of T cells via an IL-10-dependent mechanism. Human Tr1 cells have been clearly shown to maintain tolerance to self and non-self non harmful antigens, and to allo-antigens but also to infectious agents and tumor-bearing cells. In some clinical settings, transfer of ex vivo generated Tr1 cells can be envisaged as an efficient and safe approach to promote or restore immunological tolerance. One clinical trial with transfer of Tr1 cells in patients transplanted with hematopoietic stem cells is already ongoing at our institute and it will pave the road for future clinical Tr1 cell applications.