Background: The search for immune correlates of protection against Mycobacterium tuberculosis (MTB) infection in humans is limited by the focus on peripheral blood measures. Bronchoalveolar lavage (BAL) can safely be done and provides insight into cellular function in the lung where infection is first established. In this study, blood and lung samples were assayed to determine if heavily MTB exposed persons who resist development of latent MTB infection (RSTR) vs those who develop latent MTB infection (LTBI), differ in the make-up of resident BAL innate and adaptive immune cells. Methods: Bronchoscopy was performed on 21 healthy long-term Ugandan RSTR and 25 LTBI participants. Immune cell distributions in BAL and peripheral blood were compared by differential cell counting and flow cytometry. Results: The bronchoscopy procedure was well tolerated with few adverse reactions. Differential macrophage and lymphocyte frequencies in BAL differed between RSTR and LTBI. When corrected for age, this difference lost statistical significance. BAL CD4+ and CD8+ T cells were almost entirely composed of effector memory T cells in contrast to PBMC, and did not differ between RSTR and LTBI. BAL NKT, gamma-delta T cells and NK cells also did not differ between RTSR and LTBI participants. There was a marginally significant increase (p=0.034) in CD8 T effector memory cells re-expressing CD45RA (TEMRA) in PBMC of LTBI vs RSTR participants. Conclusion: This observational case-control study comparing unstimulated BAL from RSTR vs LTBI, did not find evidence of large differences in the distribution of baseline BAL immune cells. PBMC TEMRA cell percentage was higher in LTBI relative to RSTR suggesting a role in the maintenance of latent MTB infection. Functional immune studies are required to determine if and how RSTR and LTBI BAL immune cells differ in response to MTB.

中文翻译：

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乌干达成年人抗支气管肺泡灌洗液中的免疫细胞与产生潜伏结核分枝杆菌感染的那些抵抗

背景：寻找针对结核分枝杆菌的免疫相关保护因子对人类（MTB）感染的重点在于对外周血测量的限制。可以安全地进行支气管肺泡灌洗（BAL），并深入了解最初建立感染的肺细胞功能。在这项研究中，对血液和肺部样品进行了分析，以确定抵抗潜在MTB感染（RSTR）的MTB暴露者与潜在MTB感染（LTBI）的抵抗者在居民BAL天生和适应性方面的构成是否存在差异免疫细胞。方法：对21名健康的长期乌干达RSTR和25名LTBI参与者进行了支气管镜检查。通过差异细胞计数和流式细胞术比较了BAL和外周血中的免疫细胞分布。结果：支气管镜检查程序耐受良好，不良反应极少。RAL和LTBI之间的BAL巨噬细胞和淋巴细胞频率有所不同。校正年龄后，这种差异失去了统计学意义。与PBMC相比，BAL CD4 +和CD8 + T细胞几乎完全由效应记忆T细胞组成，在RSTR和LTBI之间没有差异。在RTSR和LTBI参与者之间，BAL NKT，γ-δT细胞和NK细胞也没有差异。LTBI与RSTR参与者的PBMC中重新表达CD45RA（TEMRA）的CD8 T效应记忆细胞有少量显着增加（p = 0.034）。结论：该观察性病例对照研究比较了RSTR和LTBI的未刺激BAL，未发现基线BAL免疫细胞分布存在较大差异的证据。相对于RSTR，LTBI中的PBMC TEMRA细胞百分比更高，表明在维持潜在的MTB感染中起作用。需要进行功能性免疫研究，以确定RSTR和LTBI BAL免疫细胞是否以及如何响应MTB。