Mycobacterium tuberculosis growth control by lung macrophages and CD8 cells from patient contacts
Mycobacterium tuberculosis growth control by lung macrophages and CD8 cells from patient contacts
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DOI：
10.1164/rccm.200503-411oc
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发表时间：
2006-01-15
影响因子：
24.7
通讯作者：
Schwander, SK
中科院分区：
文献类型：
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作者：
Carranza, C;Juárez, E;Schwander, SK
理论基础：活动性肺结核患者的健康家庭接触者(HHC)暴露于结核分枝杆菌(Mtb)的产气性接触，从而使保护性局部免疫研究成为可能。目的：评价肺泡巨噬细胞(AM)和自体外周血中CD8和CD8 T细胞介导的Mtb生长控制在HHC和健康未暴露的社区对照对象(CCS)中的作用。方法：将Mtb株H37Ra和H(37)Rv分别以0.1和1的倍数感染AM，并在第1、4和7天检测MTB集落形成单位。在CCS中，未观察到CD8T细胞对结核分枝杆菌生长控制的贡献。在HHC和CCS中，CD4T细胞并不增加结核分枝杆菌的生长控制。在AM和AM/CD8、AM/CD4共培养中，干扰素-γ、一氧化氮和肿瘤坏死因子被确定为Mtb生长控制的潜在介质。在HHC和CCS中，AM/CD8共培养细胞产生的干扰素-γ是AM/CD8共培养的两倍(p<；0.05)。在第4天和第7天，HHC的AM产生的一氧化氮增加，而CCS的AM则检测不到NO。干扰素-γ和硝酸浓度与结核分枝杆菌生长控制无相关性。HHC的AM/CD8共培养细胞的肿瘤坏死因子水平显著高于CCS的AM/CD8共培养细胞(p<；0.05)。结论：HHC中产气性Mtb暴露可导致Mtb特异性效应CD8 T细胞的扩张，从而限制自体AM中Mtb的生长。
Rationale: Healthy household contacts (HHCs) of patients with active pulmonary tuberculosis are exposed aerogenically to Mycobacterium tuberculosis (Mtb), thus permitting the study of protective local immunity. Objectives: To assess alveolar macrophage (AM) and autologous blood CD4 and CD8 T-cell-mediated Mtb growth control in HHCs and healthy, unexposed community control subjects (CCs).Methods: AMs were infected with Mtb strains H37Ra and H(37)Rv at multiplicities of infection 0.1 and 1. Mtb colony-forming units were evaluated on Days 1, 4, and 7.Main Results: CD8 T cells from HHCs in 1:1 cocultures with AMs significantly (p < 0.05) increased Mtb growth control by AMs. In CCs, no detectable contribution of CD8 T cells to Mtb growth control was observed. CD4 T cells did not increase Mtb growth control in HHCs or in CCs. IFN-gamma, nitric oxide, and tumor necrosis factor were determined as potential mediators of Mtb growth control in AMs and AM/CD8 and AM/CD4 cocultures. IFN-gamma production in AM/CD4 was twofold higher than that in AM/CD8 cocultures in both HHCs and CCs (p < 0.05). Nitric oxide production from AMs of HHCs increased on Days 4 and 7 and was undetectable in AMs from CCs. IFN-gamma and nitric acid concentrations and Mtb growth control were not correlated. Tumor necrosis factor levels were significantly increased in AM/CD8 cocultures from HHCs compared with AM/CD8 cocultures from CCs (p < 0.05).Conclusion: Aerogenic exposure to Mtb in HHCs leads to expansion of Mtb-specific effector CD8 T cells that limit Mtb growth in autologous AMs.