Cyclophosphamide uncovers two separate macrophage subpopulations with opposite immunogenic potential and different patterns of monokine production.

As shown previously, thioglycollate-induced peritoneal macrophages consist of two subpopulations which differ morphologically and functionally. When tagged with trinitrophenyl hapten (TNP), one macrophage subpopulation induced in vivo effector cells (Th1) of contact sensitivity (CS) reaction, while the other induced suppressor T cells (Ts) which inhibit CS and are highly sensitive to the in vivo action of cyclophosphamide (CY). Our present experiments show that CY-resistant (Th inducers) and CY-sensitive macrophages (Ts inducers) differ also in the spectrum of biologically relevant molecules which they secrete when stimulated by LPS. Thus macrophages which preferentially induce Th1 cells have a cytokine pattern IL-1LOW, IL-6HIGH, TNF-alpha LOW, while macrophages which recruit Ts cells are IL-1HIGH, IL-6LOW, TNF-alpha HIGH. TH1 inducers produced also somewhat better PGE2 then Ts inducers. Production of reactive nitrogen intermediates (NO/NO2-) was similar in both groups of macrophages. The reasons for the differential effect of CY on these two populations is not clear at present, although it is known that CY metabolites can bind to sulfhydryl groups on antigen presenting cells (APC) and thereby up- or downregulate the antigen presenting capacities of separate subpopulations of APC.