Circumvention of natural killer cell and T-cell mediated allogeneic target killing with tacrolimus (FK506) in small bowel transplantation related graft-vs-host disease.

The role of simultaneous donor-specific transfusion of unprocessed cellular bone marrow (BM) together with solid organ transplantation, a postulated concept to achieve long-term graft acceptance, was investigated in an experimental setting of semiallogeneic transplantation of parental small bowel (SBTx) to F1 hybrids. The established graft-vs-host (GvH) model revealed that simultaneous transfer of SB/BM substantially enhanced GvH-mediated immune responses in recipient target organs, e.g. skin, gut, and liver. In comparison to isolated SBTx, animal survival decreased from 16.1 (+/- 0.9) to 10.1 (+/- 0.8) days after additional BM transfusion, P < 0.001. Severe tissue injury of GvH-susceptible target organs in the setting of simultaneous SB and BMTx was associated with significant changes in recruitment and tissue distribution of NKR-P1+ cells during the GvH-related proliferative immune response. Tacrolimus effectively suppressed these initial events and prevented recipient animals from clinically and histologically observed damage caused by GvH disease.