ACUTE, LETHAL GRAFT-VERSUS-HOST DISEASE IN AN F-1-HYBRID MODEL USING GRAFTS FROM PARENTAL-STRAIN, T-CELL RECEPTOR-DELTA GENE KNOCKOUT DONORS

gamma delta T cells have been implicated in the pathogenesis of acute graft-versus-host disease (GVHD). We therefore performed experiments t o determine whether mortality from GVHD is reduced in C57BL/6xDBA/2 F- 1-hybrid (BDF1-hybrid) mice when parental strain, T-cell receptor-delt a (TCR delta) knockout (KO) donors are used. We compared mortality, we ight loss, interferon-gamma (IFN-gamma) production and cytotoxic activ ity in recipients of either wild-type or TCR delta KO grafts. In both groups there was significant weight loss and an identical level of mor tality. Elevated IFN-gamma levels were present in both groups, but rec ipients of TCR delta KO grafts produced twice as much as recipients of wild-type grafts. Elevated natural killer (NK) and NK-like activity w as also seen in both. These results demonstrate that TCR delta KO graf ts can induce GVHD as severe as that seen in recipients of wild-type g rafts, a finding that is at odds with studies demonstrating reduced mo rtality when gamma delta T cells are purged from donor mice. We sugges t that the inconsistency may lie in the higher levels of IFN-gamma see n with TCR delta KO grafts and that the protection afforded by the abs ence of gamma delta T cells in the graft is overwhelmed by the higher levels of IFN-gamma.