CD4+CD25+ regulatory T cells in hematopoietic stem cell transplantation.
Allogeneic hematopoietic stem cell transplantation (SCT) is a well-established treatment modality for malignant and nonmalignant hematologic diseases. High-dose radio- and/or chemotherapy eradicate the hematopoietic system of the patient and induce sufficient immunosuppression to enable donor stem cell engraftment. The replacement of the recipient's immune system with that of the donor significantly contributes to the success of this treatment, since donor immune cells facilitate stem cell engraftment, provide protection from infections, and eliminate residual malignant or nonmalignant host hematopoiesis, thereby protecting from disease relapse in patients transplanted for leukemia or lymphoma (graft-versus-leukemia effect, GVL). Mediators of these beneficial effects are mature T cells within the stem cell graft. However, donor T cells can also attack host tissues and induce a life-threatening syndrome called graft-versus-host disease (GVHD). The challenge of allogeneic SCT is to find a balance between beneficial and harmful T cell effects, which at present is only insufficiently achieved by the use of immunosuppressive drugs. In the future, it might be possible to replace or support such medications by using the intrinsic regulatory capacity of the transplanted immune system, as represented by T cell subpopulations with suppressive activity, such as CD4+ CD25+ regulatory T (Treg) cells. In various mouse model systems, these cells have been shown to suppress GVHD while preserving the GVL effect. As the characterization of their human counterparts is rapidly progressing, their application in allogeneic SCT might soon be explored in clinical trials.
Hoffmann
P
P
Institute of Immunology, University Regensburg, Regensburg, Germany.
Ermann
J
J
Edinger
M
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*
D015375:Receptors, Interleukin-2