Induction of proliferation in vitro of resting human natural killer cells: IL 2 induces into cell cycle most peripheral blood NK cells, but only a minor subset of low density T cells.

Abstract

We report that resting human peripheral blood natural killer (NK) cells proliferate in response to recombinant interleukin 2 (rIL 2), and addition of irradiated lymphoblastoid B cells significantly increase their proliferative response. Interaction of IL 2 with the Tac IL 2 receptor expressed on activated NK cells is necessary to maintain continued growth of these cells. Experiments in which NK cell mitosis is prevented by colchicine show that the majority of peripheral blood NK cells are induced into the first cell cycle over a 6-day culture period in the presence of rIL 2. The addition of the irradiated lymphoblastoid B cell line, Daudi, to colchicine blocked cultures does not increase the proportion of cells entering cell cycle in response to rIL 2 alone. In limiting dilution analysis, only 1/1700 B73.1+ cells grow clonally in response to rIL 2. The frequency of clonal growth of NK cells in response to irradiated Daudi cells alone is minimal, whereas the addition of irradiated Daudi cells to rIL 2 stimulated cultures resulted in a 10-fold increase in clonal frequency compared with the cultures in rIL 2 alone. Therefore, Daudi cells may act by maintaining continuous proliferation of the NK cells originally responsive to IL 2. Unlike NK cells, only a minimal proportion of peripheral blood T cells proliferate in response to IL 2. These IL 2 responsive T cells are characterized by a lower bouyant density than the majority of peripheral blood T cells. These results indicate physiologic differences between peripheral blood resting NK and T cells in their ability to be induced to cycle. IL 2 is a growth factor for both cell types, but although the presence of the growth factor is sufficient for quiescent NK cells to be induced into cycle, T cells require antigenic or other mitogenic stimuli to respond to IL 2. The small proportion of light density IL 2 responsive T cells might represent in vivo activated T cells.