Respiratory Infection Group, Liverpool School of Tropical Medicine, Pembroke Place, L3 5QA, Liverpool, UK.
Thorax. 2011 May;66(5):375-82. doi: 10.1136/thx.2010.153825. Epub 2011 Feb 25.
HIV-infected adults are at an increased risk of lower respiratory tract infections. HIV infection impairs systemic acquired immunity, but there is limited information in humans on HIV-related cell-mediated immune defects in the lung.
To investigate antigen-specific CD4(+) T cell responses to influenza virus, Streptococcus pneumoniae and Mycobacterium tuberculosis antigens in bronchoalveolar lavage (BAL) and peripheral blood between HIV-infected individuals and HIV-uninfected Malawian adults.
We obtained BAL fluid and blood from HIV-infected individuals (n=21) and HIV-uninfected adults (n=24). We determined the proportion of T cell subsets including naive, memory and regulatory T cells using flow cytometry, and used intracellular cytokine staining to identify CD4(+) T cells recognising influenza virus-, S pneumoniae- and M tuberculosis-antigens.
CD4(+) T cells in BAL were predominantly of effector memory phenotype compared to blood, irrespective of HIV status (p<0.001). There was immune compartmentalisation with a higher frequency of antigen-specific CD4(+) T cells against influenza virus, S pneumoniae and M tuberculosis retained in BAL compared to blood in HIV-uninfected adults (p<0.001 in each case). Influenza virus- and M tuberculosis-specific CD4(+) T cell responses in BAL were impaired in HIV-infected individuals: proportions of total antigen-specific CD4(+) T cells and of polyfunctional IFN-γ and TNF-α-secreting cells were lower in HIV-infected individuals than in HIV-uninfected adults (p<0.05 in each case).
BAL antigen-specific CD4(+) T cell responses against important viral and bacterial respiratory pathogens are impaired in HIV-infected adults. This might contribute to the susceptibility of HIV-infected adults to lower respiratory tract infections such as pneumonia and tuberculosis.
HIV 感染者发生下呼吸道感染的风险增加。HIV 感染会损害系统性获得性免疫，但关于 HIV 相关的肺细胞介导免疫缺陷，人类的信息有限。
研究 HIV 感染者和未感染 HIV 的马拉维成年人支气管肺泡灌洗液（BAL）和外周血中针对流感病毒、肺炎链球菌和结核分枝杆菌抗原的抗原特异性 CD4(+) T 细胞反应。
我们从 HIV 感染者（n=21）和未感染 HIV 的成年人（n=24）中获得 BAL 液和血液。我们使用流式细胞术确定 T 细胞亚群的比例，包括幼稚、记忆和调节性 T 细胞，并使用细胞内细胞因子染色来鉴定识别流感病毒、肺炎链球菌和结核分枝杆菌抗原的 CD4(+) T 细胞。
与血液相比，BAL 中的 CD4(+) T 细胞主要表现为效应记忆表型，无论 HIV 状态如何（p<0.001）。存在免疫区室化，与未感染 HIV 的成年人的血液相比，BAL 中针对流感病毒、肺炎链球菌和结核分枝杆菌的抗原特异性 CD4(+) T 细胞频率更高（每种情况均 p<0.001）。HIV 感染者中 BAL 中的流感病毒和结核分枝杆菌特异性 CD4(+) T 细胞反应受损：与未感染 HIV 的成年人相比，HIV 感染者中总抗原特异性 CD4(+) T 细胞的比例以及 IFN-γ 和 TNF-α 分泌的多功能细胞的比例较低（每种情况均 p<0.05）。
HIV 感染者对重要的病毒性和细菌性呼吸道病原体的 BAL 抗原特异性 CD4(+) T 细胞反应受损。这可能导致 HIV 感染者易患下呼吸道感染，如肺炎和肺结核。
