Induction of cytotoxicity by interleukin-2 in T gamma-lymphoproliferative disorders

We have studied 7 patients with T gamma-lymphoproliferative disorders, in whom 78-88% of circulating nonadherent lymphocytes had the morphology of large granular lymphocytes (LGL) as assessed by light and transmission electron microscopy. The main common features of the membrane phenotype of these LGL expansions included expression of T3, HNK-1 and AB8.28. Other monoclonal antibody-defined surface markers of LGL (OKM1, B73.1, N901) were variably expressed or absent in these patients. Patients' LGL had little or no natural killer (NK) activity but mediated antibody-dependent cellular cytotoxicity (ADCC). Exposure to interferons (type B or gamma) for 20-72 hr resulted in no appreciable induction of cytolytic activity. In contrast, culture in the presence of interleukin-2 (IL-2) for 3 days resulted in the expression of strong cytolytic activity in all the patients tested against an NK-susceptible (K562) and an NK-resistant (Daudi) target. The expression of T3 antigen, the low levels or lack of native NK activity and the induction of consistent cytotoxicity by prolonged exposure to IL-2 led us to suggest that the cells expanding in these subjects are related to the effectors involved in lymphokine-activated killer (LAK) activity.