BCG, the only vaccine licensed against tuberculosis, demonstrates variable efficacy in humans. Recent preclinical studies highlight the potential for mucosal BCG vaccination to improve protection. Lung tissue-resident memory T cells reside within the parenchyma, potentially playing an important role in protective immunity to tuberculosis. We hypothesised that mucosal BCG vaccination may enhance generation of lung tissue-resident T cells, affording improved protection against Mycobacterium tuberculosis. In a mouse model, mucosal intranasal (IN) BCG vaccination conferred superior protection in the lungs compared to the systemic intradermal (ID) route. Intravascular staining allowed discrimination of lung tissue-resident CD4⁺ T cells from those in the lung vasculature, revealing that mucosal vaccination resulted in an increased frequency of antigen-specific tissue-resident CD4⁺ T cells compared to systemic vaccination. Tissue-resident CD4⁺ T cells induced by mucosal BCG displayed enhanced proliferative capacity compared to lung vascular and splenic CD4⁺ T cells. Only mucosal BCG induced antigen-specific tissue-resident T cells expressing a PD-1⁺ KLRG1^- cell-surface phenotype. These cells constitute a BCG-induced population which may be responsible for the enhanced protection observed with IN vaccination. We demonstrate that mucosal BCG vaccination significantly improves protection over systemic BCG and this correlates with a novel population of BCG-induced lung tissue-resident CD4⁺ T cells.

中文翻译：

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粘膜 BCG 疫苗接种提供的增强保护与抗原特异性肺组织驻留 PD-1+ KLRG1- CD4+ T 细胞的存在有关。

BCG 是唯一获得许可的抗结核疫苗，在人体中显示出不同的功效。最近的临床前研究强调了粘膜 BCG 疫苗接种改善保护的潜力。肺组织驻留记忆 T 细胞位于实质内，可能在结核病的保护性免疫中发挥重要作用。我们假设粘膜 BCG 疫苗接种可以增强肺组织驻留 T 细胞的生成，从而提供更好的针对结核分枝杆菌的保护。在小鼠模型中，与全身皮内 (ID) 途径相比，粘膜鼻内 (IN) BCG 疫苗接种在肺部提供了更好的保护。血管内染色可区分肺组织驻留 CD4 ⁺来自肺血管系统中的 T 细胞表明，与全身疫苗接种相比，粘膜疫苗接种导致抗原特异性组织驻留 CD4 ^{+ T 细胞的频率增加。与肺血管和脾脏 CD4 +} T 细胞相比，粘膜 BCG 诱导的组织驻留 CD4 ⁺ T 细胞显示出增强的增殖能力。^{只有粘膜 BCG 诱导表达 PD-1 +} KLRG1 ^-的抗原特异性组织驻留 T 细胞细胞表面表型。这些细胞构成了 BCG 诱导的群体，这可能是通过 IN 疫苗接种观察到的增强保护作用的原因。我们证明粘膜 BCG 疫苗接种显着提高了对全身 BCG 的保护，这与 BCG 诱导的肺组织驻留 CD4 ⁺ T 细胞的新群体相关。