Abel L C, Rizzo L V, Ianni B, Albuquerque F, Bacal F, Carrara D, Bocchi E A, Teixeira H C, Mady C, Kalil J, Cunha-Neto E
Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil.
J Autoimmun. 2001 Aug;17(1):99-107. doi: 10.1006/jaut.2001.0523.
One-third of all Trypanosoma cruzi -infected patients eventually develop chronic Chagas' disease cardiomyopathy (CCC), a particularly lethal inflammatory dilated cardiomyopathy, where parasites are scarce and heart-infiltrating mononuclear cells seem to be the effectors of tissue damage. Since T. cruzi is a major inducer of interleukin-12 production, the role of inflammatory cytokines in the pathogenesis of CCC was investigated. We assayed cytokine production by peripheral blood mononuclear cells (PBMC) from CCC and asymptomatic T. cruzi -infected (ASY) individuals, as well as by T cell lines from endomyocardial biopsies from CCC patients. PBMC from CCC and ASY patients produced higher IFN-gamma levels than normal (N) individuals in response to B13 protein and phytohaemagglutinin PHA; IFN-gamma high responders (> or =1 ng/ml) were 2-3 fold more frequent among CCC patients than ASY individuals. Conversely, IL-4 production in response to the same stimuli was suppressed among T. cruzi -infected patients. The frequency of PHA-induced IFN gammaproducing cells on PBMC was significantly higher among CCC than ASY and N individuals. IFN-gamma and TNF-alpha were produced by ten out of ten PHAstimulated T cell lines from CCC patients; IL-2 and IL-10 were produced by four out of ten and one out of ten lines, respectively; IL-4, IL-1alpha, IL-1beta, IL-6 and IL-12 were undetectable. Our results suggest that CCC and ASY patients may respond differentially to the IFN-gamma-inducing stimulus provided by T. cruzi infection. Given the T(1)-type cytokine profile of heart-infiltrating T cell lines from CCC patients, the ability to mount a vigorous IFN-gamma response may play a role on the differential susceptibility to CCC development.
所有感染克氏锥虫的患者中有三分之一最终会发展为慢性恰加斯病性心肌病（CCC），这是一种特别致命的炎症性扩张型心肌病，其中寄生虫稀少，浸润心脏的单核细胞似乎是组织损伤的效应器。由于克氏锥虫是白细胞介素-12产生的主要诱导剂，因此研究了炎性细胞因子在CCC发病机制中的作用。我们检测了CCC患者和无症状克氏锥虫感染（ASY）个体外周血单核细胞（PBMC）以及CCC患者心内膜活检的T细胞系产生细胞因子的情况。CCC和ASY患者的PBMC在对B13蛋白和植物血凝素PHA的反应中产生的IFN-γ水平高于正常（N）个体；在CCC患者中，IFN-γ高反应者（≥1 ng/ml）的频率是ASY个体的2至3倍。相反，在克氏锥虫感染患者中，对相同刺激的IL-4产生受到抑制。CCC患者的PBMC上PHA诱导的IFN-γ产生细胞的频率显著高于ASY和N个体。来自CCC患者的十个PHA刺激的T细胞系中有十个产生了IFN-γ和TNF-α；分别有十分之四和十分之一的细胞系产生了IL-2和IL-10；未检测到IL-4、IL-1α、IL-1β、IL-6和IL-12。我们的结果表明，CCC和ASY患者对克氏锥虫感染提供的IFN-γ诱导刺激可能有不同反应。鉴于CCC患者心脏浸润T细胞系的T1型细胞因子谱，产生强烈IFN-γ反应的能力可能在对CCC发展的不同易感性中起作用。
