The proliferation and life-span of rat large granular lymphocytes: effects of cytokines.

Pulse labeling of large granular lymphocytes (LGL) with [3H]thymidine for 1 h in vitro showed that 1%-7% of LGL were in S phase in the blood, spleen and liver of unstimulated euthymic and athymic rats as scored with autoradiography. Repetitive injections of [3H]thymidine over 2-7 days revealed that about half of the blood and spleen LGL had formed by division of precursors during this week. Stimulation of rats with the interferon inducer poly(I).poly(C) increased the proportion of S phase LGL rapidly and simultaneously in the blood, spleen and liver, so that by 20 h after stimulation ca 30% of LGL were in the S phase in these organs. This LGL proliferation was accompanied by an increased number of LGL in all three compartments 48-96 h after poly(I).poly(C) injection. Blood LGL cultured in cell impermeable diffusion chambers in the peritoneal cavity of poly(I).poly(C)-stimulated rats exhibited enhanced natural killer (NK) activity but no proliferative response, indicating that mature LGL were not induced to undergo blastogenesis by poly(I).poly(C) in vivo. Pretreatment of NK cells with rat interferon (IFN-alpha/beta) and with human recombinant interleukin 2 (rIL 2) in vitro, showed that these two cytokines, when combined, had opposing effects on NK activity and proliferation: whereas rIL 2 inhibited the IFN-induced augmentation in NK activity, IFN inhibited the rIL 2-induced LGL proliferation.