Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation

Acute graft-versus-host disease (aGVHD) is still a major obstacle in clinical allogeneic bone marrow (BM) transplantation. CD4(+)CD25(+) regulatory T (T(reg)) cells have recently been shown to suppress proliferative responses of CD4(+)CD25(-) T cells to alloantigenic stimulation in vitro and are req...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of experimental medicine 2002-08, Vol.196 (3), p.389-399
Main Authors: Hoffmann, Petra, Ermann, Joerg, Edinger, Matthias, Fathman, C Garrison, Strober, Samuel
Format: Article
Language:English
Subjects:
Acute Disease
Animals
Bone Marrow Transplantation - immunology
CD4 Antigens - analysis
Graft vs Host Disease - prevention & control
Interleukin-10 - physiology
Lymphocyte Activation
Lymphocyte Culture Test, Mixed
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Receptors, Interleukin-2 - analysis
T-Lymphocyte Subsets - immunology
Transplantation, Homologous
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Acute graft-versus-host disease (aGVHD) is still a major obstacle in clinical allogeneic bone marrow (BM) transplantation. CD4(+)CD25(+) regulatory T (T(reg)) 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-2(b)) 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-2(d)) hosts in vivo. The addition of the CD4(+)CD25(+) T(reg) 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 T(reg) cells were of donor, but not host, origin. Our results demonstrate that the balance of donor-type CD4(+)CD25(+) T(reg) and conventional CD4(+)CD25(-) T cells can determine the outcome of aGVHD.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20020399