Alloreactivity of natural killer cells in allogeneic liver transplantation

Background. The cytolytic attack of natural killer (NK) cells is blocked by recognition of the idiotypic phenotype of certain polymorphisms in HLA cla ss I molecules, specifically by HLA-C alleles (Asn(77), Lys(80) or Ser(77), Asn(80)) or HLA-Bw4 allotypes. Because liver allograft rejection is associ ated closer with mismatch in HLA class I than class II, we investigated the role of NK cells in acute hepatic allograft rejection in vivo/in vitro. Methods. The HLA pattern was typed with serological and polymerase chain re action (PCR) techniques. In 31 liver transplantations, mononuclear cells fr om donor spleen and peripheral blood of recipients (before/after transplant ation) were cultured in mixed lymphocyte cultures (MLC), MLC-derived effect or cells were analyzed by flow cytometry and tested in Cr-51-release assays . Results. Patients with NK allospecific constellations tended to have higher numbers of NK cells in peripheral blood during the first 4 weeks after tra nsplantation, and patients' lymphocytes stimulated with donor cells had a s ignificantly higher cytotoxic activity on days 14 and 21 compared with pati ents without NK allospecificity. However, acute rejection occurred with sim ilar frequency in both groups (31% with allospecific constellations vs. 40% without). Moreover, acute rejection episodes were not associated with an i ncrease in Mt cells in vivo or enhanced cytotoxicity of NK cells to donor t arget cells. Conclusions. Under standard immunosuppressive therapy, NK allospecific cons tellations did not seem play a major role in acute hepatic allograft reject ion. Strategies to prevent or treat NK allospecific constellations after li ver transplantation are not likely to reduce the incidence or severity of a cute allograft rejection.