02274nas a2200373   4500000000100000008004100001260005500042653002400097653004400121653003100165653003100196653002300227653002000250653001400270653001100284653002100295653001900316653001700335653002400352653002500376653001300401100001200414700001300426700001500439700001200454700001000466700001300476245008600489856008000575300001000655490000600665520121500671022001401886       2011                            d  c2011 NovbPublic Library of ScienceaSan Francisco10aAntigens, Bacterial10aAntigens, Differentiation, T-Lymphocyte10aCD4-Positive T-Lymphocytes10aCD8-Positive T-Lymphocytes10aCell Proliferation10aDendritic Cells10aGranzymes10aHumans10aInterferon-gamma10aInterleukin-1210aLipopeptides10aMicrobial Viability10aMycobacterium leprae10aPerforin1 aMaeda Y1 aTamura T1 aFukutomi Y1 aMukai T1 aKai M1 aMakino M00aA lipopeptide facilitate induction of Mycobacterium leprae killing in host cells.  uhttp://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0001401  ae14010 v53 a<p>Little is known of the direct microbicidal activity of T cells in leprosy, so a lipopeptide consisting of the N-terminal 13 amino acids lipopeptide (LipoK) of a 33-kD lipoprotein of Mycobacterium leprae, was synthesized. LipoK activated M. leprae infected human dendritic cells (DCs) to induce the production of IL-12. These activated DCs stimulated autologous CD4+ or CD8+ T cells towards type 1 immune response by inducing interferon-gamma secretion. T cell proliferation was also evident from the CFSE labeling of target CD4+ or CD8+ T cells. The direct microbicidal activity of T cells in the control of M. leprae multiplication is not well understood. The present study showed significant production of granulysin, granzyme B and perforin from these activated CD4+ and CD8+ T cells when stimulated with LipoK activated, M. leprae infected DCs. Assessment of the viability of M. leprae in DCs indicated LipoK mediated T cell-dependent killing of M. leprae. Remarkably, granulysin as well as granzyme B could directly kill M. leprae in vitro. Our results provide evidence that LipoK could facilitate M. leprae killing through the production of effector molecules granulysin and granzyme B in T cells.</p>  a1935-2735