Balaji K N, Schwander S K, Rich E A, Boom W H
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
J Immunol. 1995 Jun 1;154(11):5959-68.
Alveolar macrophages form the first line of defense against inhaled droplets containing Mycobacterium tuberculosis by controlling mycobacterial growth and regulating T cell responses. CD4+ and gamma delta T cells, two major T cell subsets activated by M. tuberculosis, require accessory cells for activation. However, the ability of alveolar macrophages to function as accessory cells for T cell activation remains controversial. We sought to determine the ability of alveolar macrophages to serve as accessory cells for resting (HLA-DR-, IL-2R-) and activated (HLA-DR+, IL-2R+) gamma delta T cells in response to M. tuberculosis and its Ag, and to compare accessory cell function for gamma delta T cells of alveolar macrophages and blood monocytes obtained from the same donor. Alveolar macrophages were found to serve as accessory cells for both resting and activated gamma delta T cells in response to M. tuberculosis Ag. At high alveolar macrophage to T cell ratios (> 3:1), however, expansion of resting gamma delta T cells was inhibited by alveolar macrophages. The inhibition of resting gamma delta T cells by alveolar macrophages was dose-dependent, required their presence during the first 24 h, and was partially overcome by IL-2. Alveolar macrophages did not inhibit activated gamma delta T cells even at high accessory cell to T cell ratios, and alveolar macrophages functioned as well as monocytes as accessory cells. Monocytes were not inhibitory for either resting or activated gamma delta T cells. These findings support the following model. In the normal alveolus the alveolar macrophage to T cell ratio is > or = 9:1, and therefore the threshold for resting gamma delta T cell activation is likely to be high. Once a nonspecific inflammatory response occurs, such as after invasion by M. tuberculosis, this ratio is altered, favoring gamma delta T cell activation by alveolar macrophages.
肺泡巨噬细胞通过控制分枝杆菌生长和调节T细胞反应，形成抵御含有结核分枝杆菌的吸入飞沫的第一道防线。CD4+和γδ T细胞是被结核分枝杆菌激活的两个主要T细胞亚群，它们需要辅助细胞来激活。然而，肺泡巨噬细胞作为T细胞激活辅助细胞的能力仍存在争议。我们试图确定肺泡巨噬细胞作为辅助细胞，对静止的（HLA-DR-、IL-2R-）和活化的（HLA-DR+、IL-2R+）γδ T细胞针对结核分枝杆菌及其抗原的反应能力，并比较肺泡巨噬细胞和来自同一供体的血液单核细胞作为γδ T细胞辅助细胞的功能。发现肺泡巨噬细胞作为辅助细胞，可促进静止的和活化的γδ T细胞对结核分枝杆菌抗原的反应。然而，在肺泡巨噬细胞与T细胞比例较高（>3:1）时，静止γδ T细胞的扩增受到肺泡巨噬细胞的抑制。肺泡巨噬细胞对静止γδ T细胞的抑制是剂量依赖性的，在前24小时需要它们的存在，并且部分可被IL-2克服。即使在辅助细胞与T细胞比例较高时，肺泡巨噬细胞也不抑制活化的γδ T细胞，并且肺泡巨噬细胞作为辅助细胞的功能与单核细胞一样好。单核细胞对静止的或活化的γδ T细胞均无抑制作用。这些发现支持以下模型。在正常肺泡中，肺泡巨噬细胞与T细胞的比例≥9:1，因此静止γδ T细胞激活的阈值可能很高。一旦发生非特异性炎症反应，如结核分枝杆菌入侵后，该比例会改变，有利于肺泡巨噬细胞激活γδ T细胞。
