Evidence that development of severe cardiomyopathy in human Chagas' disease is due to a thl-specific immune response
Evidence that development of severe cardiomyopathy in human Chagas' disease is due to a thl-specific immune response
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DOI：
10.1128/iai.71.3.1185-1193.2003
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发表时间：
2003-03-01
影响因子：
3.1
通讯作者：
Correa-Oliveira, R
中科院分区：
文献类型：
--
作者：
Gomes, JAS;Bahia-Oliveira, LMG;Correa-Oliveira, R
研究了白细胞介素10（IL-10）和γ干扰素（IFN-γ）在人类恰加斯病病理发展中的作用。基于外周血单核细胞（PBMC）培养物上清液中该细胞因子的分泌水平，鉴定了两类患者，IFN-γ的低生产者和高生产者。83%的不同程度的心脏病（CARD）患者和59%的不确定形式的疾病（IND）患者被确定为高IFN-γ产生者。被归类为低IFN-γ产生者的IND患者的PBMC分泌的IL-10量显着高于其他组的患者。流式细胞术分析表明，在IND组的PBMC中，大多数IL-10产生细胞是单核细胞（CD 14（高+）细胞），而在CARD组中，IFN-γ的主要来源是T淋巴细胞（CD 3（+）CD 4（+）细胞）。这些结果表明，CD 3（+）CD 4（+）细胞产生IFN-γ与恰加斯病发病率之间存在关联，而巨噬细胞/单核细胞产生IL-10导致IND患者免疫应答的调节。我们推测，针对克氏锥虫抗原的IFN-γ的加剧产生有利于CARD患者产生强烈的Th 1应答，从而导致心脏病的进展。
The role of interleukin 10 (IL-10) and gamma interferon (IFN-gamma) on the development of pathology in human Chagas' disease was investigated. Two categories of patients, low and high producers of IFN-gamma, were identified based on the levels of secretion of this cytokine in the supernatant of peripheral blood mononuclear cell (PBMC) cultures. Eighty-three percent of the patients presenting with cardiac disease (CARD) of different degrees and 59% of the patients with the indeterminate form of disease (IND) were identified as high IFN-gamma producers. PBMC from IND patients classified as low IFN-gamma producers secreted significantly higher amounts of IL-10 than did those from other groups. Flow cytometry analysis demonstrated that in PBMC from the IND group, the majority of the IL-10-producing cells were monocytes (CD14(High+) cells), whereas in the CARD group, the major sources of IFN-gamma were T lymphocytes (CD3(+) CD4(+) cells). These results suggest an association between the production of IFN-gamma by CD3(+) CD4(+) cells and morbidity in Chagas' disease, whereas the production of IL-10 by macrophages/monocytes leads to regulation of the immune response in IND patients. We hypothesize that an exacerbated production of IFN-gamma against Trypanosoma cruzi antigens favors the development of a strong Th1 response in CARD patients, which leads to progression of heart disease.