Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Immunity. 2011 May 27;34(5):807-19. doi: 10.1016/j.immuni.2011.03.022. Epub 2011 May 19.
Cell-mediated adaptive immunity is critical for host defense, but little is known about T cell behavior during delivery of effector function. Here we investigate relationships among antigen presentation, T cell motility, and local production of effector cytokines by CD4+ T cells within hepatic granulomas triggered by Bacille Calmette-Guérin or Mycobacterium tuberculosis. At steady-state, only small fractions of mycobacteria-specific T cells showed antigen-induced migration arrest within granulomas, resulting in low-level, polarized secretion of cytokines. However, exogenous antigen elicited rapid arrest and robust cytokine production by the vast majority of effector T cells. These findings suggest that limited antigen presentation and/or recognition within granulomas evoke a muted T cell response drawing on only a fraction of the host's potential effector capacity. Our results provide new insights into the regulation of host-protective functions, especially how antigen availability influences T cell dynamics and, in turn, effector T cell function during chronic infection.
细胞介导的适应性免疫对于宿主防御至关重要，但对于效应功能传递期间 T 细胞行为知之甚少。在这里，我们研究了卡介苗或结核分枝杆菌引发的肝肉芽肿内 CD4+T 细胞中抗原呈递、T 细胞迁移和效应细胞因子局部产生之间的关系。在稳态下，只有一小部分结核分枝杆菌特异性 T 细胞在肉芽肿内表现出抗原诱导的迁移阻滞，导致细胞因子的低水平极化分泌。然而，外源性抗原迅速诱导绝大多数效应 T 细胞的阻滞和强烈的细胞因子产生。这些发现表明，在肉芽肿内有限的抗原呈递和/或识别会引发微弱的 T 细胞反应，仅利用宿主潜在效应能力的一小部分。我们的研究结果为宿主保护性功能的调节提供了新的见解，特别是抗原可用性如何影响 T 细胞动力学，并进而影响慢性感染期间效应 T 细胞的功能。
