A novel type of human T cell clone with highly potent natural killer-like cytotoxicity divorced from large granular lymphocyte morphology.

Interleukin 2-dependent cloned lymphocytes derived from an allogeneic HLA class II-mismatched but class I-matched mixed lymphocyte culture were screened for cytotoxic activity on target cell lines known to be susceptible or resistant to lysis by natural killer (NK) cells. Of 24 clones, eight were found to display NK-like cytotoxicity. Two manifested extremely high cytotoxicity levels (50% lysis of K562 at an effector to target ratio of 1:1), whereas the remainder were only moderately active (about 20% lysis at 25:1). NK-like clones were studied with regard to cell surface markers defined by monoclonal antibodies, as well as for their morphologic and cytochemical characteristics, and were compared with clones displaying different functions. The moderately active NK-like clones exhibited characteristic large granular lymphocyte morphology (many azurophilic granules, indented nuclei, high cytoplasm to nucleus ratio, and a basophilic peripheral cytoplasmic zone). This was, however, also characteristic of the majority of lymphocyte clones displaying functions other than NK. Surprisingly, the two clones with high NK-like activity did not exhibit large granular lymphocyte morphology, with few granules, round nuclei, and low cytoplasm to nucleus ratio. The T3, T9, T10, and T11 markers, as well as HLA-DR determinants, were expressed on their surfaces, but in contrast to the other clones, they did not display OKT4-, OKT8-, or OKM1-defined antigens. No distinction between them was possible on the basis of a cytochemical profile in relation to their function, because all clones were positive for acid phosphatase, either focal or dispersed and negative for nonspecific esterase or chloracetate esterase. The highly active lytic clones were, however, distinguished by an exceptionally rapid growth rate in culture (cell doubling time: 9 hr as compared to 30 to 40 hr, as usually required). These results demonstrate two different types of human NK-active lymphocytes with remarkably disparate lytic capacity, cell surface markers, and morphology.