Donor-type CD4+CD25+ Regulatory T Cells Suppress Lethal Acute Graft-Versus-Host Disease after Allogeneic Bone Marrow Transplantation
By P. Hoffmann, J. Ermann, M. Edinger, C. Fathman, S. Strober. Journal of Experimental Medicine, 2002
1,179 citations recorded by the source corpus.
Acute graft-versus-host disease (aGVHD) is still a major obstacle in clinical allogeneic bone marrow (BM) transplantation. CD4+CD25+ regulatory T (Treg) cells have recently been shown to suppress proliferative responses of CD4+CD25− T cells to alloantigenic stimulation in vitro and are required for ex vivo tolerization of donor T cells, which results in their reduced potential to induce aGVHD. Here we show that CD4+CD25+ T cells isolated from the spleen or BM of donor C57BL/6 (H-2b) mice that have not been tolerized are still potent inhibitors of the alloresponse in vitro and of lethal aGVHD induced by C57BL/6 CD4+CD25− T cells in irradiated BALB/c (H-2d) hosts in vivo. The addition of the CD4+CD25+ Treg cells at a 1:1 ratio with responder/inducer CD4+CD25− T cells resulted in a >90% inhibition of the mixed leukocyte reaction and marked protection from lethal GVHD. This protective effect depended in part on the ability of the transferred CD4+CD25+ T cells to secrete interleukin 10 and occurred if the Treg cells were of donor, but not host, origin. Our results demonstrate that the balance of donor-type CD4+CD25+ Treg and conventional CD4+CD25− T cells can determine the outcome of aGVHD.
Subfields: Hematology, Immunology
View Paper: https://www.semanticscholar.org/paper/1e6bf9fbb76f5524da8daf91c3d5fa1b2367e57a
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In Immunology
Citations in the corpus
- First-in-man clinical results of the treatment of patients with graft versus host disease with human ex vivo expanded CD4+CD25+CD127- T regulatory cells. (2009, background): “The purity of transferred Tregs seems to be crucial for the procedure as the contamination with effectors hampers both expansion phase [11] and protection from GvHD [5].”
- Decidual and peripheral blood CD4+CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases. (2004, background): “…cells, CD4+CD25+ Treg cells play a role in the induction of tolerance (Sakaguchi et al., 1995; Taylor et al., 2001; Beacher-Allan et al., 2001; Jonuleit et al., 2001; Levings et al., 2001; Ng et al., 2001; Stephens et al., 2001; Cohen et al., 2002; Hoffmann et al., 2002; Word and Sakaguchi, 2003).”
- Continuous Activation of Autoreactive CD4+ CD25+ Regulatory T Cells in the Steady State (2003, background): “For instance, we and others have shown that transfer of T reg could be used to control autoimmune diabetes (11, 12), solid allograft rejection (13‐15), or graft versus host disease (7, 9, 16 ) in mice.”
- Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. (2011, background): “In murine models of HSCT across MHC barriers, CD4CD25 Tregs suppressed lethal GvHD (9) and favoured post-transplant immune reconstitution when coinfused with conventional T cells (Tcons) (10).”