Lipscomb M F, Huffnagle G B, Lovchik J A, Lyons C R, Pollard A M, Yates J L
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235-9072.
Arch Pathol Lab Med. 1993 Dec;117(12):1225-32.
Understanding how lung immunity develops against pulmonary pathogens should lead to more rational approaches in vaccine design and to the use of recombinant cytokines in lung disease. T lymphocytes are central to the development of effective immune responses; therefore, understanding how lung immunity develops will require a study of how and where T cells respond to respiratory antigens. Our laboratory has helped define the phenotype and function of lung dendritic cells, which likely play an essential role in stimulating naive T cells to respond to antigens. We found that both interstitial and alveolar macrophages can regulate the function of these cells, the former to enhance activity, the latter to suppress. In addition, we developed a murine pulmonary infection model using the fungus, Cryptococcus neoformans, in which T-cell-mediated immunity is essential for effective host clearance of the organism. The role of T cells in this model is to recruit and activate effector cells to resolve the lung infection; both CD4 and CD8 T-cell subsets are required for optimal effector cell recruitment. These studies are summarized as examples of current approaches to understanding pulmonary immunity.
了解肺部免疫系统如何抵御肺部病原体，有望为疫苗设计带来更合理的方法，并推动重组细胞因子在肺部疾病中的应用。T淋巴细胞是有效免疫反应发展的核心；因此，要了解肺部免疫是如何发展的，就需要研究T细胞如何以及在何处对呼吸道抗原作出反应。我们的实验室已助力明确了肺树突状细胞的表型和功能，这些细胞可能在刺激初始T细胞对抗原作出反应方面发挥着至关重要的作用。我们发现，间质巨噬细胞和肺泡巨噬细胞均可调节这些细胞的功能，前者增强活性，后者抑制活性。此外，我们利用新型隐球菌开发了一种小鼠肺部感染模型，在该模型中，T细胞介导的免疫对于机体有效清除该病原体至关重要。T细胞在该模型中的作用是招募并激活效应细胞以解决肺部感染；最佳效应细胞招募需要CD4和CD8 T细胞亚群共同参与。这些研究作为当前理解肺部免疫方法的示例进行了总结。
