@article{2024,
  keywords = {CD40 Antigens, CD40 Ligand, Cell Membrane, Cells, Cultured, Cytokines, Humans, Immunity, Cellular, Interleukin-12, Leprosy, lepromatous, Leprosy, Tuberculoid, Ligands, Membrane Glycoproteins, Monocytes, Mycobacterium leprae, RNA, Messenger, Th1 Cells, Up-Regulation},
  author = {Yamauchi P S and Bleharski J R and Uyemura K and Kim J and Sieling P A and Miller A and Brightbill H and Schlienger K and Rea T H and Modlin R L},
  title = {A role for CD40-CD40 ligand interactions in the generation of type 1 cytokine responses in human leprosy.},
  abstract = {<p>The interaction of CD40 ligand (CD40L) expressed by activated T cells with CD40 on macrophages has been shown to be a potent stimulus for the production of IL-12, an obligate signal for generation of Th1 cytokine responses. The expression and interaction of CD40 and CD40L were investigated in human infectious disease using leprosy as a model. CD40 and CD40L mRNA and surface protein expression were predominant in skin lesions of resistant tuberculoid patients compared with the highly susceptible lepromatous group. IL-12 release from PBMC of tuberculoid patients stimulated with Mycobacterium leprae was partially inhibited by mAbs to CD40 or CD40L, correlating with Ag-induced up-regulation of CD40L on T cells. Cognate recognition of M. leprae Ag by a T cell clone derived from a tuberculoid lesion in the context of monocyte APC resulted in CD40L-CD40-dependent production of IL-12. In contrast, M. leprae-induced IL-12 production by PBMC from lepromatous patients was not dependent on CD40L-CD40 ligation, nor was CD40L up-regulated by M. leprae. Furthermore, IL-10, a cytokine predominant in lepromatous lesions, blocked the IFN-gamma up-regulation of CD40 on monocytes. These data suggest that T cell activation in situ by M. leprae in tuberculoid leprosy leads to local up-regulation of CD40L, which stimulates CD40-dependent induction of IL-12 in monocytes. The CD40-CD40L interaction, which is not evident in lepromatous leprosy, probably participates in the cell-mediated immune response to microbial pathogens.</p>},
  year = {2000},
  journal = {Journal of immunology (Baltimore, Md. : 1950)},
  volume = {165},
  pages = {1506-12},
  month = {2000 Aug 01},
  issn = {0022-1767},
  url = {http://www.jimmunol.org/content/165/3/1506.full.pdf+html},
  doi = {10.4049/jimmunol.165.3.1506},
  language = {eng},
}