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 c ells in murine recipients transplanted with MHC-mismatched marrow grafts. S tudies were conducted using ex vivo-activated gamma delta T cells because t his was a more clinically relevant strategy, and these cells have been show n 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 cup T cells alone. In contrast, when the administration of naive alpha beta T cells was delayed for 2 wk po st-BMT, survival was significantly enhanced in mice transplanted with BM pl us activated gamma delta T cells vs those given marrow cells alone. Mitigat ion of GVHD by activated gamma delta T cells occurred only at high doses (1 50 x 10(6)) and was a unique property of gamma delta T cells, as activated alpha beta T cells were incapable of ameliorating the subsequent developmen t of GVHD. Protection from GVHD was not due to the direct inhibition of nai ve alpha beta T cells by gamma delta T cells, Rather, gamma delta T cells m ediated this effect indirectly through donor BM derived alpha beta T cells that acted as the proximate regulatory population responsible for the decre ase in GVH reactivity. Collectively, these data demonstrate that activated gamma delta T cells are capable of modulating the ability of MHC-incompatib le nontolerant alpha beta T cells to cause GVHD after allogeneic BMT.