T-CELL CYTOKINES MAY CONTROL THE BALANCE OF FUNCTIONALLY DISTINCT MACROPHAGE POPULATIONS

As monocytes differentiate into mature macrophages, subsets emerge tha t exhibit stimulatory, suppressive or phagocytic potential. These func tionally distinct subsets can be discriminated using monoclonal antibo dies RFD1 and RFD7. As examples of all these subsets have been repeate dly identified within the macrophage pool in a variety of organs the o verall functional capacity of this pool will depend on the relative ba lance of these subpopulations. This study investigates whether this ba lance present in mature macrophage populations can be regulated by the local influence of T-cell-derived cytokines. The dose-dependent effec t of cytokines interferon-gamma (IFN-gamma), interleukins (IL) IL-2, I L-4 and IL-10 on the phenotype and function of monocyte-derived macrop hages was determined. Subsets of mature cells were quantified by ident ifying RFD1(+) RFD7(-) stimulatory cells (D1(+)); RFD1(-) RFD7(+) phag ocytes (D7(+)) and RFD1(+) RFD7(+) suppressive cells (D1/D7(+)). IFN-g amma and IL-4 increased the relative proportions of D1(+) stimulatory cells and upregulated HLA-DR expression. IFN-gamma also increased the capacity of the mature macrophage pool to stimulate T-cell proliferati on. IL-10 reduced the proportions of D1(+) stimulatory cells while pro moting the differentiation of D7(+) phagocytes and D1/D7(+) suppressiv e cells. IL-10 induced changes also reduced the functional capacity of the mature populations to stimulate T cells in auto and allogenic mix ed lymphocyte reactions (MLR). IL-2 had no effect on differentiation o f monocytes. Thus IL-4 and IFN-gamma are seen to induce the developmen t of stimulatory macrophages while IL-10 promotes differentiation of m onocytes to mature phagocytes and suppressive macrophages. It is concl uded that mature macrophage phenotype is 'plastic' and under the contr ol of T-cell-derived mediators. Furthermore, within the differentiatin g monocytes, phenotypic change appears to carry with it functional cha nge, thus retaining the relationship between antigen expression and ac tivity in the mature macrophage populations.