Activation of lymphocytes inhibits human monocyte to macrophage differentiation

Tissue macrophages (MAC) differentiate from circulating blood monocytes (MO ) during a maturation step that is of crucial importance for their function al competence. In vitro a similar process of maturation can be observed, if MO are cultured in the presence of serum. In the work presented here, we s how that activated lymphocytes can interfere with MAC differentiation. Rest ing lymphocytes have only marginal influence upon MO to MAC transition in v itro. However, if cells are activated by the lectins PV,PWM or ConA or by d ouble-stranded RNA (polyinosinic-polycytidylic acid, pI:C), normal MAC matu ration is suppressed: MO stay small and do not acquire MAC maturation-assoc iated surface molecules like carboxypeptidase M (CPM, determined by antibod y MAX. 1) or CD84 (determined by antibody MAX.3). This phenomenon can be in duced by small numbers of lymphocytes and can be transmitted by soluble fac tors in cultures stimulated with ConA or PWM. IFN-gamma is present in these conditioned media and partially suppresses MAC maturation but cannot fully substitute for the conditioned media. On the contrary, in pI:C stimulated Cultures, suppression of MAC differentiation is dependent on cell-cell cont act. In conclusion, activated lymphocytes are able to suppress the terminal differentiation of MAC by several pathways depending on the mode of lympho cyte stimulation.