Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4+ T-Cell Responses to Mycobacteria
Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4+ T-Cell Responses to Mycobacteria
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DOI：
10.1164/rccm.201405-0864oc
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发表时间：
2014-10-15
影响因子：
24.7
通讯作者：
Mwandumba, Henry C.
中科院分区：
文献类型：
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作者：
Jambo, Kondwani C.;Banda, Dominic H.;Mwandumba, Henry C.
理由：接受抗逆转录病毒治疗(ART)的艾滋病毒感染者患肺结核(TB)的风险仍然高于未感染艾滋病毒的人。这种易感性的增加可能是由于在HIV感染的初学者中观察到的肺泡巨噬细胞(AM)功能和/或分枝杆菌特异性的肺泡CD4(+)T细胞反应的损害所致。目的：通过吞噬体蛋白分解来评估ART是否与AM功能和肺泡CD4(+)T细胞对分枝杆菌的反应的改善有关。方法：抽取健康成人、35名HIV未感染的ART、25名HIV感染的ART和50名接受ART治疗的HIV无症状的成年人，进行外周血和支气管肺泡灌洗(BAL)。用荧光微球检测AM的吞噬体蛋白降解。通过细胞内细胞因子染色检测分枝杆菌特异性的CD4(+)T细胞反应。测量和主要结果：接受ART治疗的HIV感染者血浆HIV病毒载量低于ART初治者，而外周血中的CD4(+)T细胞数高于ART初治者。接受抗逆转录病毒治疗4年以上的患者AM蛋白分解和总分枝杆菌特异性Th1、CD4(+)T细胞反应与未感染HIV的对照组相似，但接受抗逆转录病毒治疗不到4年的受试者反应受损。在所有接受抗逆转录病毒治疗的患者中，总的流感特异性Th1、CD4(+)T细胞反应是完整的。结论：接受抗逆转录病毒治疗4年以下的HIV感染者肺泡巨噬细胞和分枝杆菌特异的肺泡CD4(+)T细胞反应受损，这可能是抗逆转录病毒治疗中HIV感染者结核病高风险的部分原因。应该研究加强抗逆转录病毒疗法以改善肺免疫细胞功能和降低启动抗逆转录病毒疗法的艾滋病毒感染成人中结核病的高发病率的策略。
Rationale: HIV-infected persons on antiretroviral therapy (ART) remain at higher risk of pulmonary tuberculosis (TB) than HIV-uninfected individuals. This increased susceptibility may be caused by impairment of alveolar macrophage (AM) function and/or mycobacteria-specific alveolar CD4(+) T-cell responses observed in HIV-infected ART-naive adults.Objectives: To determine whether ART was associated with improvement in both AM function, assessed by phagosomal proteolysis, and alveolar CD4(+) T-cell responses to Mycobacterium in HIV-infected individuals.Methods: Peripheral blood was drawn and bronchoalveolar lavage (BAL) performed on healthy, 35 HIV-uninfected, 25 HIV-infected ART-naive, and 50 HIV-infected ART-treated asymptomatic adults. Phagosomal proteolysis of AM was assessed with fluorogenic beads. Mycobacteria-specific CD4(+) T-cell responses were measured by intracellular cytokine staining.Measurements and Main Results: HIV-infected adults on ART exhibited lower plasma HIV viral load and higher blood CD4(+) T-cell count than ART-naive adults. AM proteolysis and total mycobacteria-specific Th1 CD4(+) T-cell responses in individuals on ART for greater than or equal to 4 years were similar to HIV-uninfected control subjects but those on ART for less than 4 years had impaired responses. Total influenza-specific alveolar Th1 CD4(+) T-cell responses were intact in all individuals receiving ART. In contrast, BAL and blood mycobacteria-specific polyfunctional CD4(+) T-cell responses were impaired in adults on ART irrespective of duration.Conclusions: AM and mycobacteria-specific alveolar CD4(+) T-cell responses in HIV-infected adults on ART for less than 4 years are impaired and may partly explain the high risk of TB in HIV-infected individuals on ART. Strategies to augment ART to improve lung immune cell function and reduce the high incidence of TB in HIV-infected adults who initiate ART should be investigated.