CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host
Author: ["Matthias Edinger","Petra Hoffmann","Joerg Ermann","Kathryn Drago","C Garrison Fathman","Samuel Strober","Robert S Negrin"]
Publication: Nature Medicine
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Abstract
Mature donor T cells cause graft-versus-host disease (GVHD), but they are also the main mediators of the beneficial graft-versus-tumor (GVT) activity of allogeneic bone marrow transplantation. Suppression of GVHD with maintenance of GVT activity is a desirable outcome for clinical transplantation. We have previously shown that donor-derived CD4+CD25+ regulatory T cells inhibit lethal GVHD after allogeneic bone marrow transplantation across major histocompatibility complex (MHC) class I and II barriers in mice. Here we demonstrate that in host mice with leukemia and lymphoma, CD4+CD25+ regulatory T cells suppress the early expansion of alloreactive donor T cells, their interleukin-2-receptor (IL-2R) α-chain expression and their capacity to induce GVHD without abrogating their GVT effector function, mediated primarily by the perforin lysis pathway. Thus, CD4+CD25+ T cells are potent regulatory cells that can separate GVHD from GVT activity mediated by conventional donor T cells.
Cite this article
Edinger, M., Hoffmann, P., Ermann, J. et al. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med 9, 1144–1150 (2003). https://doi.org/10.1038/nm915
