Role of the regulatory T cells CD4+CD25+ and mesenchymal marrow stem cells in suppressing a graft versus host reaction

Abstract

A graft versus host disease (GVHD) is one of the most serious complications occurring after allogeneic marrow cell transplantation. The investigation of the immune mechanisms responsible for the development of an acute GVHD has revealed a critical role of the regulatory T cells CD4+CD25+Foxp3+ that are responsible for the suppression of the function of effector rejection mechanisms, including the inhibition of the cytotoxic T lymphocytes CD8+, Т- helper cells CD4+CD25, natural killer cells and others that damage the host cells. Animal experiments have indicated the leading role of regulatory T cells in the initiation of GVHD. A number of human studies have analysed a correlation between the levels of the regulatory T cells CD4+CD25+Foxp3+ in the graft and/or blood of a recipient and the further occurrence of acute or chronic GVHD. The severity of an allogeneic GVHD is inversely related to the low expression of Foxp3.Besides regulatory T cells, mesenchymal stem cells (MSCs) have a significant immunosuppressive effect that has been demonstrated in the animal experiments and in the clinical trials in patients. MSCs do not only prevent the development of a GVHD, but may be used for the treatment of a just incipient process. In the opinion of a number of authors, MSCs prevent the development of a GVHD by directly affecting the induction of regulatory T cells in vivo.

Keywords

• graft versus host reaction
• mesenchymal stem cells
• regulatory t cells