Donor gamma delta T lymphocytes promote allogeneic engraftment across the major histocompatibility barrier in mice.

T cells that express the alpha beta T-cell receptor are thought to be the T-cell population primarily responsible for facilitating alloengraftment. The role of gamma delta + T cells that comprise only a minority of mature T cells in promoting allogeneic engraftment, however, has not been extensively studied. The purpose of this study was to determine whether gamma delta T cells were capable of facilitating alloengraftment in murine recipients of major histocompatibility complex-mismatched marrow grafts. We developed a model where engraftment of C57BL/6 x 129/F2(H-2b) marrow in sublethally irradiated (800 cGy) recipients (AKR/J, H-2k) is dependent on the presence of mature donor T cells in the marrow graft. In this model, donor T-cell engraftment was significantly augmented by as few as 1 x 10(5) alpha beta T cells. The role of gamma delta T cells was then investigated using transgenic donors (C57BL/6 x 129 background) in which a portion of the T-cell receptor-beta chain gene was deleted by gene targeting so that these mice lack alpha beta T cells. Addition of 10 x 10(5) naive gamma delta T cells to T-cell depleted marrow grafts was required to significantly increase alloengraftment, although donor T cells averaged < 50% of total splenic T cells. To determine whether higher doses of gamma delta T cells would improve donor engraftment and eradicate residual host T cells, gamma delta T cells were ex vivo expanded with a gamma delta T-cell-specific mono-clonal antibody and interleukin-2 and then transplanted into irradiated recipients. Transplantation of > or = 160 x 10(6) activated gamma delta T cells was necessary to consistently and significantly augment donor cell chimerism and enhance hematopoietic reconstitution when compared to control mice, but host T cells persisted in these chimeras. Addition of 2.5 x 10(4) mature alpha beta T cells, which alone were incapable of facilitating engraftment, to T-cell depleted marrow grafts containing 160 x 10(6) activated gamma delta T cells resulted in long-term (> 100 day) complete donor engraftment, indicating that limiting numbers of alpha beta T cells were required in the marrow graft for the eradication of residual host T cells. Using serial weight curves and B-cell reconstitution as end points, clinically significant graft-versus-host disease was not observed in these chimeras under these experimental conditions. These data show that, whereas less potent than alpha beta T cells, gamma delta T cells are able to promote engraftment and enhance hematopoietic reconstitution in allogeneic marrow transplant recipients.