Production by stimulated macrophages of factors depressing lymphocyte transformation.

Abstract

MACROPHAGES can inhibit the responses of lymphocytes to a variety of stimuli. The presence of excessive numbers of normal macrophages led to inhibition of antibody formation by cultured mouse lymphoid cells1–3. Normal rat spleen cell suspensions responded better to non-specific stimulation by Gram-negative bacterial lipopolysaccharide (endotoxin) after being freed of macrophages, but the response was reduced again by the addition of macrophages4. Spleen cells from mice injected with Coryne-bacterium parvum5,6 or subjected to a graft-versus-host (GvH) reaction6,7 showed decreased antibody formation7 and decreased responsiveness to phytohaemagglutinin (PHA) or allogeneic lymphocytes5 when cultured in vitro. Such mice possess activated macrophages8,9. Their spleen cell responses were restored, at least in part, by removal of macrophages6,7. Attempts to demonstrate the production of soluble inhibitors by macrophages in vitro have generally been unsuccessful6,7,10. Mouse serum can inhibit primary antibody formation11–14 and mitogen-induced transformation of T lymphocytes and B lymphocytes in cultures of mouse spleen cells ; we have suggested (ref. 15 ; D. S. N. and C. N. Shneider, unpublished) that the factor responsible for the latter effect may be produced by macrophages. Here I present evidence that mouse peritoneal macrophages activated in vivo produce a potent inhibitor of lymphocyte transformation when cultured in vitro.