CORRELATION BETWEEN GRAFT-VERSUS-HOST INDUCED IMMUNOSUPPRESSION AND HOST NATURAL-KILLER-CELL ACTIVITY IN SMALL-BOWEL TRANSPLANTATION

The occurrence of graft-versus-host disease (GvHD) following small bow el transplantation (SBTx) can be tuned by the recipient's initial natu ral killer (NK) cell activity, which modifies the immunogeneic balance between donor and host immunocompetent cells. This study was aimed to investigate the role of host NK cells on the incidence and severity o f GVHD following SBTx. Intraperitoneal administration of 50 mu l ascit es fluid of the highly specific anti-NKR-P1 monoclonal antibody (mAb) 3.2.3 into F1 recipient animals on three consecutive days prior to SBT x was performed to suppress NK activity in F1 hybrids. In vivo treatme nt with 3.2.3 mAb effectively depleted recipient NK activity for at le ast 10 days in spleens and mesenteric lymph nodes of F1 hosts. In cont rast to nontreated F1 recipients, all 3.2.3 mAb-pretreated F1 animals suffered from severe signs of GvHD, and the mean survival time was dec reased significantly from 16.0 +/- 0.9 days to 11.0 +/- 0.8 days (p < 0.01) in nontreated and NKR-P1-depleted F1 animals, respectively. Othe r sequelae included earlier onset of GvH manifestations, pronounced da mage of primary and secondary lymphatic organs, substantial increase i n spleen index, and lower CD4(+)/CD8(+) ratios over the course of prog ressing GvHD. Our results underline the important immunoregulatory rol e of NK cells as a first defensive line acting on the alloreactivity o f donor-derived immunocompetent cells in this model of solid organ tra nsplantation.