Lymphokine-activated killer cells derived from murine bone marrow: age-associated difference in precursor cell populations demonstrated by response to interferon.

We have previously demonstrated that the majority of precursor cells of lymphokine-activated killer (LAK) cells in spleens from both young and old mice reside in the natural killer (NK) cell or pre-NK cell populations. In the present study, we examined the induction of LAK cell activity in bone marrow cells from young and old mice and its modulation by interferon (IFN). Bone marrow cells from either young (6-9 weeks) or old (20-26 months) mice were cultured with 1000 U/ml of human recombinant interleukin 2 (rIL-2) for 5 days. The cells were harvested and tested for their cytotoxicity against NK-resistant fresh tumor cells (MCA-102) in a 51Cr release assay. As with spleen cells, bone marrow cells from old and young mice developed comparable levels of activity. Phenotypic analysis showed that virtually all of the LAK precursor cells were asialo GM1+ and most of the effector cells expressed Thy-1, regardless of the age of the mice. Inclusion of IFN-gamma during the culture with rIL-2 augmented the activity induced in bone marrow of young mice, but, in contrast, inhibited the generation of LAK activity from bone marrow cells of old mice. These results demonstrate a differential sensitivity of LAK precursor (or pre-NK) cells of old and young mice to interferon.