Regulatory T Cells Expressing IL10 and Their Role in Transplantation

For 20 years it is known from transplant experiments that a cell population exists within the T cell compartment which is able to exert suppressive/regulatory functions after immunosup-pressive treatment.43 Further experiments have clearly shown that tolerogenic cells which have been generated under the umbrella of monoclonal antibody induced tolerance can be transferred into naïve animals by adoptive transfer.44,45 Since then, many groups have investigated the role of regulatory T cells in autoimmune diseases and transplantation (for review see refs. 15,46-52). It becomes more and more clear that different cell types within the regulatory cell compartment may have regulatory/suppressive effects dependent on the expression of "regulatory" molecules. The majority of these cell populations express IL-10 which is a clear indication that IL-10 plays an important role in the generation/maintenance of a regulatory cell phenotype. However, in many cases these cells have been generated in vivo during tolerance inducing protocols e.g., with monoclonal antibodies.53 It would be of great importance to establish methods for the generation of regulatory T cells in-vitro. First attempts have been reported by Groux et al,54 who demonstrated that CD4+ T cells subset expressing IL-10 inhibits antigen-specific T cell responses and prevents colitis upon adoptive transfer. Recently it has been shown that incubation of mixed lymphocyte reactions (MLR) with IL-10 and Transforming Growth Factor-P (TGF-P) induce alloreactive T cells with regulatory function in a GVHD-model.55 In addition to the experiments described above, experiments have been performed the generate IL-10 expressing regulatory cells by treatment with Vitamin D3 and Dexamethason. This leads to the generation of regulatory cells expressing IL-10.56

As it is now possible to generate and expand in vitro alloreactive regulatory T cells—Treg1— that are able to suppress alloreactive effector T cells in-vitro15 there is the opportunity to apply Treg in clinical situations. Presently, Roncarolo and colleagues are performing a pilot trial to test the immunoregulatory capacity of these IL-10 driven Treg1 cells for preventing acute and chronic graft-versus-host disease in haploidentical bone marrow transplantation.

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