Recent Advances in Human Natural Killer Cells

This paper reviews recent progresses on human Natural Killer (NK) cells which profoundly changed our concepts on NK cells and their functions. Regarding the ontogeny of NK cells, immature thymocyte populations (CD-3-4-16-) hav been shown to give rise to NK cells, provided suitable culture conditions. This indicates that precursor potentially capable of differentiation towards the NK cell lineage are present within the human thymus. Although NK cells lack known receptors for antigen (i.e. sIg and TCR) NK cell populations or clones were found to be capable of mediating specific recognition of allogenic cells. This specific function was clonally distributed and, more importantly, NK clones displaying different patterns of allospecificity could be isolated from single individuals. These data indicate the existence of a NK cell repertoire for alloantigen recognition. Analysis of the surface molecules identified by NK cells indicated that certain HLA alleles (e.g. HLA-Cw3) can act as specific protective elements from lysis by clones with defined specificities (e.g. specificity 2). Therefore, HLA class I molecules appear to play a central role in the NK cell-mediated functions. The finding that human NK cells express a clonally-dystributed ability to recognize alloantigens suggested the existence of distinct surface receptors. Indeed, a new family of triggering surface molecules (58 kD) has been identified by the use of monoclonal antibodies. The expression of these molecules was shown to represent a stable phenotipic property of human NK cells and to be clonally distributed. More importantly, the expression of 58 kD molecules appears to correlate with the ability to recognize given allospecificities. These data are supporting the concept that 58 kD molecules are part of receptor structures involved in the NK cell-mediated recognition.