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 cells^1–3. 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 parvum^5,6 or subjected to a graft-versus-host (GvH) reaction^6,7 showed decreased antibody formation⁷ and decreased responsiveness to phytohaemagglutinin (PHA) or allogeneic lymphocytes⁵ when cultured in vitro. Such mice possess activated macrophages^8,9. Their spleen cell responses were restored, at least in part, by removal of macrophages^6,7. Attempts to demonstrate the production of soluble inhibitors by macrophages in vitro have generally been unsuccessful^6,7,10. Mouse serum can inhibit primary antibody formation^11–14 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and B lymphocytes in cultures of mouse spleen cells ; we have suggested (ref. 15 ; D. S. N. and C. N. Shneider, unpublished) that the factor responsible for the latter effect may be produced by macrophages.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.