In vivo depletion of NKR-P1 positive cells in the recipient prior to small bowel transplantation enhances graft-versus-host disease (GvHD) in the rat

Abstract  Recent evidence for major histocompatibility complex (MHC) class I antigen-directed recognition mechanisms of natural killer cells (NKs) have revived interests in investigating non-adaptive immune responses in the framework of solid organ transplantation. A semi-allogeneic rat model of heterotopic small bowel transplantation (HSBTx) from male DA parental to male F1 hybrid rats (DA X LEW) was established to investigate the role of host NKs to attenuate graft-versus-host (GvH)-mediated immu-nosuppression and tissue injury. By use of anti-NKR-P1 monoclonal antibody (mAb) 3.2.3, host NKs were depleted effectively in vivo after triple intraperitoneal injection prior to HSBTx. In contrast to non-depleted animals, an initial lack of NK activity in F1 hosts significantly decreased the mean survival ( P < 0.01) and substantially enhanced graft-versus-host disease (GvHD)-related damage to lymphoid and non-lym-phoid target organs. These findings emphasize the important immuno-regulatory role of host NKs during the early onset of GvHD.