Upregulation of T-cell-stimulating activity of mycobacteria-infected macrophages.
Macrophages are one of the most abundant host cells to come in contact with mycobacteria. However, the infected macrophages less efficiently stimulate autologous T cells in vitro. We investigated the effect of the induction of phenotypic change of macrophages on the host cell activities by using Mycobacterium leprae as a pathogen. The treatment of macrophages with interferon-gamma (IFN-gamma), GM-CSF and interleukin-4 deprived macrophages of CD14 antigen expression but instead provided them with CD1a, CD83 and enhanced CD86 antigen expression. These phenotypic features resembled those of monocyte-derived dendritic cells (DC). These macrophage-derived DC-like cells (MACDC) stimulated autologous CD4+ and CD8+ T cells when infected with M. leprae. Further enhancement of the antigen-presenting function and CD1a expression of macrophages was observed when treated with IFN-gamma. The M. leprae-infected and -treated macrophages expressed bacterial cell membrane-derived antigens on the surface and were efficiently cytolysed by the cell membrane antigen-specific CD8+ cytotoxic T lymphocytes (CTL). These results suggest that the induction of phenotypic changes in macrophages can lead to the upregulation of host defence activity against M. leprae.
Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
H
H
Kimura
Y
Y
Maeda
F
F
Takeshita
L E
LE
Takaoka
M
M
Matsuoka
M
M
Makino
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000382:microbiology; D007918:Leprosy / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D009166:Mycobacterium leprae / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015854:Up-Regulation