Specificity and phenotype of IL-2 expanded clones of human large granular lymphocytes

Abstract

Clones of human large granular lymphocytes (LGL) derived from a single blood donor were grown in culture medium supplemented with interleukin-2 (IL-2). The source of IL-2 was the supernatant of a gibbon lymphosarcoma cell line, MLA-144. Of 89 LGL clones tested for their ability to lyse a panel of natural killer (NK)-susceptible tumor cell lines in a cytotoxicity assay, a total of 12 clones were cytotoxic, showing a heterogeneous pattern of reactivity. In contrast, all clones from T lymphocytes grown in the same conditions were consistently negative against all the targets. Four of the cytotoxic LGL clones lysed K562 and Alab and also had antibody-dependent cellular cytotoxicity (ADCC); three clones were cytotoxic only for K562; two clones were reactive only in ADCC; one lysed both the ADCC target and Alab; two lysed only Daudi. Thirty LGL clones (among which 9 demonstrated cytotoxic activity) were also studied for their surface phenotypes with monoclonal antibodies. Most of these LGL clones were OKM1+ and weakly OKT3+. Of the clones with cytotoxic activity, 55% reacted with OKT8 and OKT10 whereas among the noncytotoxic clones, 90% were OKT10+, and 10% were OKT8+. These results demonstrate diversity among cytolytic clones of LGL, supporting the hypothesis of a clonal distribution of specificity within the NK cell population.