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.
Kimura
H
H
Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
Maeda
Y
Y
Takeshita
F
F
Takaoka
L E
LE
Matsuoka
M
M
Makino
M
M
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