Alloreactivity of natural killer cells in allogeneic liver transplantation

The cytolytic attack of natural killer (NK) cells is blocked by recognition of the idiotypic phenotype of certain polymorphisms in HLA class I molecules, specifically by HLA-C alleles (Asn77, Lys80 or Ser77, Asn80) or HLA-Bw4 allotypes. Because liver allograft rejection is associated 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.

The HLA pattern was typed with serological and polymerase chain reaction (PCR) techniques. In 31 liver transplantations, mononuclear cells from donor spleen and peripheral blood of recipients (before/after transplantation) were cultured in mixed lymphocyte cultures (MLC). MLC-derived effector cells were analyzed by flow cytometry and tested in 51Cr-release assays.

Patients with NK allospecific constellations tended to have higher numbers of NK cells in peripheral blood during the first 4 weeks after transplantation, and patients' lymphocytes stimulated with donor cells had a significantly higher cytotoxic activity on days 14 and 21 compared with patients without NK allospecificity. However, acute rejection occurred with similar frequency in both groups (31% with allospecific constellations vs. 40% without). Moreover, acute rejection episodes were not associated with an increase in NK cells in vivo or enhanced cytotoxicity of NK cells to donor target cells.

Under standard immunosuppressive therapy, NK allospecific constellations did not seem play a major role in acute hepatic allograft rejection. Strategies to prevent or treat NK allospecific constellations after liver transplantation are not likely to reduce the incidence or severity of acute allograft rejection.