The Regulation of Lymphocyte Functions by the Macrophage

Macrophages may exert a regulatory influence at various stages in the life of the lymphocyte - they may influence the non-antigen-driven differentiation of lymphocytes - as exemplified by the effects on thymic differentiation; they may establish the mode and form of antigen to be presented or recognized by the lymphocyte; may regulate the lymphocyte's antigen-driven functions. Each of these critical regulatory steps needs explaining in molecular terms and integrated and placed in the context of the other regulatory functions of lymphocytes. The control of secretion of MP is an eloquent example of the molecular complexities and the intricate congrol mechanisms - internal and external - operating at each step of each regulatory process. A final comment concern the question of macrophage heterogeneity. Is the same cell performing all the functions of degradation, presentation, and secretion - or cytotoxicity? Or do we have subpopulation, each with a different role? This issue is not settled. The unitarians argue that the phagocytes pass through different stages of differentiation and that each function may become more or less prominent at each stage. Certainly, the manner in which each macrophage function is assayed can condition the outcome: for antigen presentation, one adds 1 % of macrophages to cultures of spleen cells; for cytotoxic assays, the figure is 50 to 100 macrophages per tumor cell! It is our feeling that until such time as membrane molecules are identified and used as probes for differentiation or for identification of subsets we will not resolve this issue. Along these lines, macrophages have been found to have Ia antigens (Hämmerling et al. 1975, Schwartz et al. 1976) and can be divided into two sets on the basis of the presence or absence of Ia. Dorf and I have found - by cytotoxicity - that only about 35 to 50% of peritoneal macrophages bear Ia molecules (Dorf & Uanue 1977). Exceptionally, some exudates will bear up to 75% positive cells. Neither Ia-positive nor Ia-negative macrophages change significantly after prolonged periods of culture. Whether these results indicate two defined subsets of macrophages is now being investigated.