Radiosensitivity of NK lytic activities and NK-mediated hematopoietic colony inhibition: effect of activation with IL-2 and blocking of the T-200 molecule.

Overview

NK cells are capable of a variety of effector functions including the unprimed lysis of certain tumor cell targets and the nonspecific suppression of hematopoietic colony formation. In this study we have evaluated in parallel the radiosensitivity of lytic and colony inhibitory activity (CIA) by peripheral blood lymphocytes and large granular lymphocytes before and after activation by 72-96 hr of culture in medium containing interleukin 2 (IL-2). Our results show that (1) cells exhibiting CIA and lytic activities have almost identical patterns of radioresistance both before and following activation by IL-2; (2) the amount of preculture irradiation which completely blocks IL-2-stimulated cell proliferation only minimally affects CIA and lytic activities; (3) lysis of K562 and inhibition of CFU-GM are more resistant to preculture irradiation than is the killing of NK insensitive targets; (4) both the CIA and the lytic activities of PBL, but not of LGL, can be increased by 500-1000 rad of gamma-irradiation; and (5) NK lytic activity and CIA both before and following activation by IL-2 are primarily mediated by cells bearing the NKH1A antigen. Evidence that suggests NK cells mediate both the lysis of K562 and the inhibition of myeloid cells by a common mechanism came from experiments which showed that a monoclonal antibody to the T-200 molecule (13.3) could block both activities.