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.
Heystek
H C
HC
Novartis Research Institute, Vienna, Austria.
Mudde
G C
GC
Ohler
R
R
Kalthoff
F S
FS
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects*; D015232:Dinoprostone / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects*; D013601:T-Lymphocytes / Q000166:cytology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007376:Interleukin-2; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015232:Dinoprostone; D007213:Indomethacin