Naturally Occurring Cytotoxic Cells

Summary

From its beginning, the field of natural cytotoxicity has been beset by two major problems which have a direct bearing on the continuing quest for the in vivo relevance of spontaneous cytocidal mechanisms. First, the remarkable phenotypic heterogeneity of NK cells has remained until recently an intriguing open question. The second problem concerns the as yet unknown recognition mechanisms and the undefined membrane structures on the target cells. Many studies have been undertaken to define the relationship of NK cells to the three main classes of lymphoid cells: macrophages, T cells, and B cells. This problem has become amenable recently with the help of monoclonal antibodies and by cloning of effector cells. The designation of NK cells as null cells has been revised for several species. Thus, in the mouse promonocytes have been characterized as NK cells with a defined spectrum of susceptible target cells. However, other findings point to a considerable heterogeneity which shows that NK cells express Thy-1 antigens as well as Ly related antigens characteristic for the T cell lineage. Expression of the Fc receptor remains controversal since Fc receptors may be absent on some NK cells depending on their organ origin. In man, large granular lymphocytes (LGL), as a characteristic minor subpopulation, seem to account for all of the NK activity. Analysis with monoclonal antibodies revealed that malignant cells as well as normal cells which resemble LGL may express a hybrid phenotype; that is, they may show a simultaneous expression of thymus-associated and monomyelocytic-associated antigens. This finding on human cells may shed light on the unusual heterogeneity observed in mice where NK cells with monocytic and thymic phenotypes have been discerned.

No conclusive evidence has so far been provided for the in vivo operation of these cells. Cloning of effector cells, though fashionable and widely applied, has not yet resolved the Chamaeleon-like phenoyype. No conclusion can be reached on the basis of cloned cells as to the problem of clonal distribution of NK-like specificity. Phenotypic analysis by monoclonal antibodies as well as the examination of the specificity pattern of cloned cells is expected to yield some insight into these problems.