03159nas a2200457   4500000000100000008004100001260001600042653001500058653002400073653001700097653002000114653001400134653001800148653001100166653002000177653002100197653001200218653002500230653001900255653002800274653006200302653001400364653001800378100001600396700001600412700001400428700001200442700001800454700001500472700001700487700001300504700001700517700001300534700001500547700001600562245014300578300001200721490000800733520194600741022001402687       2001                            d  c2001 Nov 1510aAntibodies10aAntigens, Bacterial10aAntigens, CD10aCells, Cultured10aCytokines10aGlycoproteins10aHumans10aImmunoglobulins10aInterferon-gamma10aleprosy10aMycobacterium leprae10aRNA, Messenger10aReceptors, Cell Surface10aSignaling Lymphocytic Activation Molecule Family Member 110aTh1 Cells10aUp-Regulation1 aGarcía V E1 aQuiroga M F1 aOchoa M T1 aOchoa L1 aPasquinelli V1 aFainboim L1 aOlivares L M1 aValdez R1 aSordelli D O1 aAversa G1 aModlin R L1 aSieling P A00aSignaling lymphocytic activation molecule expression and regulation in human intracellular infection correlate with Th1 cytokine patterns.  a5719-240 v1673 a<p>Induction of Th1 cytokines, those associated with cell-mediated immunity, is critical for host defense against infection by intracellular pathogens, including mycobacteria. Signaling lymphocytic activation molecule (SLAM, CD150) is a transmembrane protein expressed on lymphocytes that promotes T cell proliferation and IFN-gamma production. The expression and role of SLAM in human infectious disease were investigated using leprosy as a model. We found that SLAM mRNA and protein were more strongly expressed in skin lesions of tuberculoid patients, those with measurable CMI to the pathogen, Mycobacterium leprae, compared with lepromatous patients, who have weak CMI against M. leprae. Peripheral blood T cells from tuberculoid patients showed a striking increase in the level of SLAM expression after stimulation with M. leprae, whereas the expression of SLAM on T cells from lepromatous patients show little change by M. leprae stimulation. Engagement of SLAM by an agonistic mAb up-regulated IFN-gamma production from tuberculoid patients and slightly increased the levels of IFN-gamma in lepromatous patients. In addition, IFN-gamma augmented SLAM expression on M. leprae-stimulated peripheral blood T cells from leprosy patients. Signaling through SLAM after IFN-gamma treatment of Ag-stimulated cells enhanced IFN-gamma production in lepromatous patients to the levels of tuberculoid patients. Our data suggest that the local release of IFN-gamma by M. leprae-activated T cells in tuberculoid leprosy lesions leads to up-regulation of SLAM expression. Ligation of SLAM augments IFN-gamma production in the local microenvironment, creating a positive feedback loop. Failure of T cells from lepromatous leprosy patients to produce IFN-gamma in response to M. leprae contributes to reduced expression of SLAM. Therefore, the activation of SLAM may promote the cell-mediated immune response to intracellular bacterial pathogens.</p>  a0022-1767