02205nas a2200433   4500000000100000008004100001260001600042653001200058653003100070653003100101653001400132653002700146653001900173653000900192653001800201653001100219653002500230653002100255653001200276653001600288653002600304653002800330653000900358653002400367653001900391653002500410100001300435700001500448700001100463700001400474700001200488700001100500700001800511245015300529300000900682490001600691520105000707022001401757       2002                            d  c2002 Feb 1510aAnimals10aCD4-Positive T-Lymphocytes10aCD8-Positive T-Lymphocytes10aCytokines10aDisease Models, Animal10aFlow Cytometry10aFoot10aGene Deletion10aHumans10aImmunohistochemistry10aInterferon-gamma10aleprosy10aLymph Nodes10aLymphocyte Activation10aMacrophages, Peritoneal10aMice10aMice, Inbred BALB C10aMice, Knockout10aMycobacterium leprae1 aAdams LW1 aScollard D1 aRay NA1 aCooper AM1 aFrank A1 aOrme I1 aKrahenbuhl JL00aThe study of Mycobacterium leprae infection in interferon-gamma gene--disrupted mice as a model to explore the immunopathologic spectrum of leprosy.  aS1-80 v185 Suppl 13 a<p>Mycobacterium leprae infection was evaluated in interferon-gamma knockout (GKO) mice. At 4 months, growth of the bacilli in the footpads of GKO mice plateaued a log(10) higher than that in control mice. Control mice exhibited mild lymphocytic and histiocytic infiltrates, whereas GKO mice developed large, unorganized infiltrates of epithelioid macrophages and scattered CD4 and CD8 T cells. Flow cytometric analysis of popliteal lymph node cells demonstrated similar profiles of T cells; however, GKO cells exhibited an elevated proliferative response to M. leprae antigen. Expression of inducible nitric oxide synthase mRNA was decreased in GKO mice, whereas macrophage inflammatory protein-1alpha and interleukin-4 and -10 mRNA expression were augmented. Control and GKO activated macrophages inhibited bacterial metabolism and produced nitrite. Thus, although deficient in an important Th1 cytokine, GKO mice possess compensatory mechanisms to control M. leprae growth and feature elements resembling mid-borderline leprosy in humans.</p>  a0022-1899