Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, South Africa.
Eur J Immunol. 2012 Jan;42(1):147-57. doi: 10.1002/eji.201141927.
HIV-1-infected people have an increased risk of developing extrapulmonary tuberculosis (TB), the immunopathogenesis of which is poorly understood. Here, we conducted a detailed immunological analysis of human pericardial TB, to determine the effect of HIV-1 co-infection on the phenotype of Mycobacterium tuberculosis (MTB)-specific memory T cells and the role of polyfunctional T cells at the disease site, using cells from pericardial fluid and blood of 74 patients with (n = 50) and without (n = 24) HIV-1 co-infection. The MTB antigen-induced IFN-γ response was elevated at the disease site, irrespective of HIV-1 status or antigenic stimulant. However, the IFN-γ ELISpot showed no clear evidence of increased numbers of antigen-specific cells at the disease site except for ESAT-6 in HIV-1 uninfected individuals (p = 0.009). Flow cytometric analysis showed that CD4+ memory T cells in the pericardial fluid of HIV-1-infected patients were of a less differentiated phenotype, with the presence of polyfunctional CD4+ T cells expressing TNF, IL-2 and IFN-γ. These results indicate that HIV-1 infection results in altered phenotype and function of MTB-specific CD4+ T cells at the disease site, which may contribute to the increased risk of developing TB at all stages of HIV-1 infection.
HIV-1 感染者发生肺外结核（TB）的风险增加，但其免疫发病机制尚不清楚。在这里，我们对人类心包 TB 进行了详细的免疫学分析，以确定 HIV-1 合并感染对结核分枝杆菌（MTB）特异性记忆 T 细胞表型的影响以及多功能 T 细胞在疾病部位的作用，使用来自 74 名患者的心包液和血液中的细胞，其中 HIV-1 合并感染患者（n=50）和未合并感染患者（n=24）。无论 HIV-1 状态或抗原刺激如何，疾病部位的 IFN-γ 反应均升高。然而，IFN-γ ELISpot 除了 HIV-1 未感染者的 ESAT-6 外（p=0.009），并没有明显证据表明疾病部位抗原特异性细胞数量增加。流式细胞术分析显示，HIV-1 感染患者的心包液中的 CD4+记忆 T 细胞表型分化程度较低，存在表达 TNF、IL-2 和 IFN-γ 的多功能 CD4+T 细胞。这些结果表明，HIV-1 感染导致疾病部位的 MTB 特异性 CD4+T 细胞表型和功能发生改变，这可能导致 HIV-1 感染的各个阶段发生 TB 的风险增加。
