Spontaneous production of colony-stimulating activity by splenic Mac-1 antigen-positive cells from autoimmune motheaten mice.

Cultured splenocytes from 3-wk-old autoimmune motheaten mice (me/me) spontaneously produced colony-stimulating activity (CSA), which stimulated the formation of bone marrow myeloid colonies. The production of CSA was not dependent on the presence of serum; this activity was not produced by spleen cells from their phenotypically normal littermates (+/-) or from other normal mouse strains. The peak level of CSA occurred early during the culture period, and within 48 hr the activity was markedly diminished. Cell fractionation studies demonstrated that cells expressing Mac-1 antigen produce CSA and are most likely to be mononuclear phagocytes. The unusual proliferative capacity in vitro of splenic mononuclear phagocytes from motheaten mice probably results from the spontaneous production of CSA by Mac-1 antigen-positive cells. Defective regulation of the production of monokines may contribute to the severity of the immunologic disease of these mutant mice.