Adoptively transferred gamma delta T cells indirectly regulate murine graft-versus-host reactivity following donor leukocyte infusion therapy in mice.
The purpose of this study was to determine whether gamma delta T cells were able to regulate graft-vs-host (GVH) reactivity mediated by alpha beta T cells in murine recipients transplanted with MHC-mismatched marrow grafts. Studies were conducted using ex vivo-activated gamma delta T cells because this was a more clinically relevant strategy, and these cells have been shown to be capable of facilitating alloengraftment without causing GVH disease (GVHD). Coadministration of activated gamma delta T cells and naive alpha beta T cells at the time of bone marrow transplantation (BMT) significantly exacerbated GVHD when compared with naive alpha beta T cells alone. In contrast, when the administration of naive alpha beta T cells was delayed for 2 wk post-BMT, survival was significantly enhanced in mice transplanted with BM plus activated gamma delta T cells vs those given marrow cells alone. Mitigation of GVHD by activated gamma delta T cells occurred only at high doses (150 x 106) and was a unique property of gamma delta T cells, as activated alpha beta T cells were incapable of ameliorating the subsequent development of GVHD. Protection from GVHD was not due to the direct inhibition of naive alpha beta T cells by gamma delta T cells. Rather, gamma delta T cells mediated this effect indirectly through donor BM-derived alpha beta T cells that acted as the proximate regulatory population responsible for the decrease in GVH reactivity. Collectively, these data demonstrate that activated gamma delta T cells are capable of modulating the ability of MHC-incompatible nontolerant alpha beta T cells to cause GVHD after allogeneic BMT.
Drobyski
W R
WR
Departments of Medicine and Biostatistics and Bone Marrow Transplant Program, Medical College of Wisconsin, Milwaukee, WI 53226, USA. bill@bmt.mcw.edu
Vodanovic-Jankovic
S
S
Klein
J
J
D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D006087:Graft vs Host Reaction / Q000235:genetics / Q000276:immunology*; D017708:Leukocyte Transfusion; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D018800:Thy-1 Antigens / Q000096:biosynthesis; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018800:Thy-1 Antigens