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Transplantation immunology has traditionally focused on adaptive, i.e., T- and B-cell reactions. More recently, natural killer (NK) cells were also recognised as playing an important role after transplantation of solid organs and haematopoietic stem cells. NK cells recognise "cell stress" induced by viral replication and tumour transformation via activating receptors, and are negatively regulated by the interaction between inhibitory molecules and autologous human leukocyte antigens (HLA). The most important inhibitory molecules belong to the family of killer cell immunoglobulin-like receptors (KIR). Differences in the inhibitory KIR/HLA interaction between stem cell donor and patient may lead to beneficial NK cell alloreactivity, resulting in specific graft-versus-tumour reactions, which occur in the absence of graft-versus-host disease. The immaturity of NK cells produced by the stem cell graft early after transplantation has led to different approaches of adoptive transfer of NK cells to further increase tumour control. The function and role of activating KIR receptors is less clear. Recent data have suggested, that activating KIR may also contribute to anti-tumour immunity after stem cell transplantation, as patients transplanted from donors carrying high numbers of activating KIR receptor genes show reduced relapse rates. In particular, protection from post-transplant disease relapse was demonstrated in transplants carried out from donors carrying the activating KIR2DS1 receptor, if the recipients also expressed the KIR2DS1 ligand HLA-C2. In conclusion, NK cells have been firmly established in the last two decades as relevant players in transplant immunology, which can critically determine the outcome of haematopoietic stem cell grafts.
