Natural killer group 2 member D cell recruitment driven by major histocompatibility complex class I chain-related antigens A and B: a possible mechanism during acute intestinal allograft rejection in the mouse.

Intestinal allograft rejection occurs frequently despite potent T-cell depletion protocols. We investigated the interaction of major histocompatibility complex class I chain-related antigens A and B (MICA/B; a ligand for natural killer [NK] cells) and NK group 2 member D (NKG2D) cells as an alternative mechanism for acute rejection (AR) of the intestinal graft. Heterotopic intestinal allotransplantation was performed from BalbC to C57Bl mice. Samples of grafted and native intestine were obtained at days 1, 3, 6, and 8 after transplantation (n = 4-6). We performed immunostaining for MICA/B and NKG2D. Moderate AR with increased crypt apoptosis was observed at day 6 and advanced AR with crypt destruction and mucosal sloughing was present by day 8. Low MICA/B levels were observed in grafted and native intestines on day 1. MICA/B expression gradually increased in the grafts during AR but not in the native intestines. The up-regulation was found mostly in the crypts. NKG2D+ cell counts that increased in the graft colocalized with MICA/B. The increase was most prominent in the crypt and villus. Together, these results suggest that MICA/B up-regulation and its subsequent interaction with the NK cells may represent an important link between innate and adaptive immune responses early after intestinal transplantation.