Further characterization of murine bone marrow-derived natural suppressor cells. Potential relationships between NS and NK/LAK activities

Murine bone marrow (BM) cells regulate a variety of immune responses via an endogenous natural suppressor (NS) activity. We demonstrate that BM-derived NS activity resides in an enriched fraction of large, low-density cells which have a high proliferative rate. Complement-dependent lysis of BM cells by antibody directed against markers of Veto and NK/LAK cells had no effect on NS activity. The BM of SCID mice and their littermate C.B-17 possessed normal NS activity. Conversely, the BM of NK-deficient C57 beige mice displayed reduced NS activity as compared to normal C57 black mice. Long-term BM cultures (LTBMC) generated in medium containing supernatants of Con A-stimulated (CAS) rat spleen cells resulted in the emergence of a population of cells which possessed NS activity greater than that of fresh BM cells. The LTBMC were also potent effectors of NK activity, as compared to fresh BM, which had little NK activity. Thus, while NS, NK/LAK, and Veto cells are all nonspecific effectors of immune suppression, the exact relationship between them is not clear.