Contribution of GM-CSF on the enhancement of the T cell-stimulating activity of macrophages.
Mycobacterium leprae is an intracellular parasitic organism that multiplies in macrophages (MØ). It inhibits the fusion of mycobacterial phagosome with lysosome and induces interleukin (IL)-10 production from macrophages. However, macrophages are heterogenous in various aspects. We examined macrophages that differentiated from monocytes using either recombinant (r) granulocyte-MØ colony-stimulating factor (GM-CSF) (these MØ are named as GM-MØ) or rMØ colony-stimulating factor (M-CSF) (cells named as M-MØ) in terms of the T cell-stimulating activity. Although both macrophages phagocytosed the mycobacteria equally, GM-MØ infected with M. leprae and subsequently treated with IFN-gamma- and CD40 ligand (L) stimulated T cells to produce interferon-gamma (IFN-gamma), but M-MØ lacked the ability to stimulate T cells. While M-MØ mounted a massive IL-10 production, GM-MØ did not produce the cytokine on infection with M. leprae. M. leprae-infected, IFN-gamma- and CD40L-treated GM-MØ expressed a higher level of HLA-DR and CD86 Ags than those of M-MØ, and expressed one of the dominant antigenic molecules of M. leprae, Major Membrane Protein-II on their surface. These results indicate that GM-CSF, but not M-CSF, contributes to the up-regulation of the T cell-stimulating activity of M. leprae-infected macrophages.
Makino
Masahiko
M
Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama, Tokyo 189-0002, Japan. mmaki@nih.go.jp
Maeda
Yumi
Y
Fukutomi
Yasuo
Y
Mukai
Tetsu
T
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D007918:Leprosy / Q000276:immunology* / Q000382:microbiology; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D009166:Mycobacterium leprae / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology*
D016753:Interleukin-10; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor