T‐cell cytokines may control the balance of functionally distinct macrophage populations

Abstract

SUMMARYAs monocytes diÂerentiate into mature macrophages, subsets emerge that exhibit stimulatory, suppressive or phagocytic potential. These functionally distinct subsets can be discriminated using monoclonal antibodies RFD1 and RFD7. As examples of all these subsets have been repeatedly identified within the macrophage pool in a variety of organs the overall functional capacity of this pool will depend on the relative balance of these subpopulations. This study investigates whether this balance present in mature macrophage populations can be regulated by the local influence of T-cell-derived cytokines. The dose-dependent eÂect of cytokines interferon-c ( IFNc), interleukins ( IL) IL-2, IL-4 and IL-10 on the phenotype and function of monocyte-derived macrophages was determined. Subsets of mature cells were quantified by identifying RFD1+ RFD7− stimulatory cells ( D1+); RFD1− RFD7+ phagocytes (D7+) and RFD1+ RFD7+ suppressive cells ( D1/D7+). IFN-c and IL-4 increased the relative proportions of D1+ stimulatory cells and upregulated HLA-DR expression. IFN-c also increased the capacity of the mature macrophage pool to stimulate T-cell proliferation. IL-10 reduced the proportions of D1+ stimulatory cells while promoting the diÂerentiation of D7+ phagocytes and D1/D7+ suppressive cells. IL-10 induced changes also reduced the functional capacity of the mature populations to stimulate T cells in auto and allogenic mixed lymphocyte reactions ( MLR). IL-2 had no eÂect on diÂerentiation of monocytes. Thus IL-4 and IFN-c are seen to induce the development of stimulatory macrophages while IL-10 promotes diÂerentiation of monocytes to mature phagocytes and suppressive macrophages. It is concluded that mature macrophage phenotype is 'plastic' and under the control of T-cell-derived mediators. Furthermore, within the diÂerentiating monocytes, phenotypic change appears to carry with it functional change, thus retaining the relationship between antigen expression and activity in the mature macrophage populations.

Differentiation of C2D Macrophage Cells after Adoptive Transfer

“…The lack of a change in so many molecules was somewhat surprising. IFN-␥ has profound effects on macrophage function and activation (2,48,52,61,66) and influences monocyte maturation (17,54,66). The increase in Gr-1 may reflect activation, as macrophage granularity tends to positively correlate with activation (10,56).…”

“…A T-cell cytokine, IFN-␥, has been shown to have profound effects on macrophage function (66), including the induction of macrophage activation (2, 52, 61), increased microbicidal activity (2,48), and increased surface expression of MHC-II (41,66). We therefore hypothesized that upon stimulation with IFN-␥, C2D macrophage cells would further alter their phenotype in vivo but would experience minimal effects in vitro.…”

Normal human dermis contains distinct populations of CD11c+BDCA-1+ dendritic cells and CD163+FXIIIA+ macrophages

“…In keeping with this, CD68 also stained both CD11c + and FXIIIA + cells. CD11b and RFD7, considered to be common macrophage markers (13,15), were present on both CD11c + and FXIIIA + cells. CD63, an MHC class II internalization antigen, marked occasional CD11c + and FXIIIA + cells in normal skin.…”

Chemotherapy ± Cetuximab Modulates Peripheral Immune Responses in Metastatic Colorectal Cancer

“…The resulting change in the Th1/Th2 balance might have effectively influenced the outcome of auto-MLR responses in these patients, which were also found to be considerably improved. This assumption is also based on previous findings which demonstrated positive and negative regulation of auto-MLR responses by Th1 and Th2 cytokines, respectively [42,43,44]. …”