03270nas a2200469   4500000000100000008004100001260001300042653001500055653001000070653000900080653001600089653001000105653001100115653001300126653002100139653001900160653001200179653002500191653002500216653002600241653001600267653002500283653001500308653001800323653003200341653001600373100001300389700001600402700001700418700001400435700001300449700001600462700001400478700001300492700001400505700001800519245009000537300001100627490000700638520214100645022001402786       2000                            d  c2000 Apr10aAdolescent10aAdult10aAged10aBCG Vaccine10aChild10aHumans10aImmunity10aInterferon-gamma10aInterleukin-1010aleprosy10aLeprosy, lepromatous10aLeprosy, Tuberculoid10aLymphocyte Activation10aMiddle Aged10aMycobacterium leprae10aSkin Tests10aT-Lymphocytes10aTumor Necrosis Factor-alpha10aVaccination1 aLima M C1 aPereira G M1 aRumjanek F D1 aGomes H M1 aDuppre N1 aSampaio E P1 aAlvim I M1 aNery J A1 aSarno E N1 aPessolani M C00aImmunological cytokine correlates of protective immunity and pathogenesis in leprosy.  a419-280 v513 a<p>The in vitro production of interferon (IFN)-gamma, interleukin (IL)-5, tumour necrosis factor (TNF)-alpha and IL-10 by blood mononuclear cells in response to whole Mycobacterium leprae and polyclonal stimulii of 23 individuals, representing a variety of conditions in relation to exposure/susceptibility to M. leprae, was assayed. In most cases, healthy household contacts of newly diagnosed multibacillary leprosy patients, designated exposed household contacts (EC), showed low-to-undetectable in vitro IFN-gamma production in addition to substantial TNF-alpha production in response to M. leprae. In contrast, peripheral blood mononuclear cells from previously exposed contacts (R) regarded as resistant-to-leprosy released low-to-moderate levels of IFN-gamma together with a mixed cytokine profile resembling a T helper (Th)0-type response. TNF-alpha/IL-10 ratios in response to M. leprae and Concanavalin A were significantly higher in EC than in R contacts suggesting a role for the TNF-alpha/IL-10 ratio in restraining mycobacteria proliferation and spreading early in infection. The cytokine profiles of leprosy patients were taken as reference points. Post-treatment lepromatous leprosy patients secreted relatively high levels of IL-10 in response to M. leprae, whereas one self-cured tuberculoid leprosy patient produced simultaneously high levels of IFN-gamma and TNF-alpha. In addition, the quantitative changes in the cytokines released by peripheral blood mononuclear cells in EC contacts after Bacille Calmette-Guérin (BCG) vaccination were investigated. Vaccination induced amplification of IFN-gamma production with a concomitant decrease in TNF-alpha/IL-10 ratios that resembled the cytokine pattern observed in R contacts. IFN-gamma production was observed in response to both a cross-reactive antigen (Ag 85) and a M. leprae-specific protein (MMP-I), which attests to a BCG nonspecific stimulation of the immune system, thereby casting these antigens as likely candidates for inclusion in a subunit vaccine against leprosy. Finally, a model for protective x pathologic response to mycobacteria is presented.</p>  a0300-9475