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- Title
CD4[sup+]CD25[sup+] regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation.
- Authors
Edinger, Matthias; Hoffmann, Petra; Ermann, Joerg; Drago, Kathryn; Fathman, C. Garrison; Strober, Samuel; Negrin, Robert S.
- Abstract
Mature donor T cells cause graft-versus-host disease (GVHD), but they are also the main mediators of the beneficial graft-versustumor (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[sup +]CD25[sup +] 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[sup +]CD25[sup +] 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[sup +]CD25[sup +] T cells are potent regulatory cells that can separate GVHD from GVT activity mediated by conventional donor T cells.
- Subjects
T cells; GRAFT versus host disease; BONE marrow transplantation
- Publication
Nature Medicine, 2003, Vol 9, Issue 9, p1144
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm915