01966nas a2200289 4500000000100000008004100001260001300042653001200055653002900067653001200096653001600108653000900124653002500133653002900158653001800187100001300205700001200218700001600230700001600246700001500262700001300277245008600290300001100376490000700387520126800394022001401662 2004 d c2004 Sep10aAnimals10aAntigen-Presenting Cells10aleprosy10aMacrophages10aMice10aMycobacterium leprae10aT-Lymphocytes, Cytotoxic10aUp-Regulation1 aKimura H1 aMaeda Y1 aTakeshita F1 aTakaoka L E1 aMatsuoka M1 aMakino M00aUpregulation of T-cell-stimulating activity of mycobacteria-infected macrophages. a278-860 v603 a

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.

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