Granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) has opposing effects on the capacity of monocytes versus monocyte‐derived dendritic cells to stimulate the antigen‐specific proliferation of a human T cell clone
GM‐CSF is widely used in combination with IL‐4 to differentiate monocytes into potent T cell stimulatory cells, referred to as monocyte‐derived dendritic cells (MoDC). These cytokines further increased the stimulatory function of MoDC when present during their incubation with antigen, as determined by the proliferative response of an allergen‐specific T cell clone. Conversely, the incubation of freshly isolated monocytes with antigen in the presence of GM‐CSF or GM‐CSF and IL‐4 strongly inhibited the specific stimulation of the T cells, compared with monocytes pulsed in the absence of cytokines. This suppression was partly due to the secretion of prostaglandin E2 (PGE2) and IL‐10 by GM‐CSF‐treated monocytes, since the combined use of indomethacin and anti‐IL‐10 antibodies during GM‐CSF incubation and antigen pulsing restored T cell growth to about 65% of control levels. As confirmed by culture supernatant transfer experiments, maximal inhibition of T cell stimulation was also dependent on the direct contact between the T cells and GM‐CSF‐treated monocytes during antigen presentation. Collectively, these results imply that GM‐CSF can either inhibit or enhance the re‐stimulation of primed T cells by antigen‐presenting monocytes or MoDC, respectively.