McMaster Immunology Research Centre, and Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
PLoS One. 2012;7(7):e41666. doi: 10.1371/journal.pone.0041666. Epub 2012 Jul 23.
Tuberculosis (TB) vaccine-induced airway luminal T cells (ALT) have recently been shown to be critical to host defense against pulmonary TB. However, the mechanisms that maintain memory ALT remain poorly understood. In particular, whether respiratory mucosal exposure to environmental agents such as endotoxin may regulate the size of vaccine-induced ALT population is still unclear. Using a murine model of respiratory genetic TB vaccination and respiratory LPS exposure, we have addressed this issue in the current study. We have found that single or repeated LPS exposure increases the number of antigen-specific ALT which are capable of robust secondary responses to pulmonary mycobacterial challenge. To investigate the potential mechanisms by which LPS exposure modulates the ALT population, we have examined the role of ALT proliferation and peripheral T cell recruitment. We have found that LPS exposure-increased ALT is not dependent on increased ALT proliferation as respiratory LPS exposure does not significantly increase the rate of proliferation of ALT. But rather, we find it to be dependent upon the recruitment of peripheral T cells into the airway lumen as blockade of peripheral T cell supplies markedly reduces the initially increased ALT. Thus, our data suggest that environmental exposure to airborne agents such as endotoxin has a profound modulatory effect on TB vaccine-elicited T cells within the respiratory tract. Our study provides a new, M.tb antigen-independent mechanism by which the respiratory mucosal anti-TB memory T cells may be maintained.
结核病（TB）疫苗诱导的气道腔 T 细胞（ALT）最近被证明对宿主防御肺部 TB 至关重要。然而，维持记忆 ALT 的机制仍知之甚少。特别是，呼吸道粘膜接触环境因子（如内毒素）是否会调节疫苗诱导的 ALT 群体的大小仍不清楚。在本研究中，我们使用呼吸基因 TB 疫苗接种和呼吸 LPS 暴露的小鼠模型解决了这个问题。我们发现，单次或重复 LPS 暴露会增加抗原特异性 ALT 的数量，这些 ALT 能够对肺部分枝杆菌的挑战产生强烈的二次反应。为了研究 LPS 暴露调节 ALT 群体的潜在机制，我们研究了 ALT 增殖和外周 T 细胞募集的作用。我们发现，LPS 暴露增加的 ALT 不依赖于 ALT 增殖的增加，因为呼吸 LPS 暴露不会显著增加 ALT 的增殖率。相反，我们发现它依赖于外周 T 细胞向气道腔的募集，因为外周 T 细胞供应的阻断显著减少了最初增加的 ALT。因此，我们的数据表明，空气传播剂（如内毒素）的环境暴露对呼吸道中的 TB 疫苗诱导的 T 细胞具有深远的调节作用。我们的研究提供了一种新的、与 M.tb 抗原无关的机制，通过该机制，呼吸道中的抗 TB 记忆 T 细胞可能得到维持。
