Beck J M, Warnock M L, Curtis J L, Sniezek M J, Arraj-Peffer S M, Kaltreider H B, Shellito J E
Respiratory Care Section, Department of Veterans Affairs Medical Center, San Francisco, California 94121.
Am J Respir Cell Mol Biol. 1991 Aug;5(2):186-97. doi: 10.1165/ajrcmb/5.2.186.
Pneumocystis carinii is the most important pulmonary pathogen in patients with the acquired immunodeficiency syndrome, but host defenses against P. carinii are not well characterized. We recently reported an experimental model of P. carinii infection, in which mice selectively depleted of CD4+ lymphocytes develop pulmonary infection after inoculation with P. carinii. In the current study, we compared lung inflammatory responses to P. carinii inoculation in CD4-depleted mice and in normal mice in order to further characterize host defenses against P. carinii. We hypothesized that depletion of CD4+ lymphocytes would prevent recruitment and activation of inflammatory cells in the lungs of these mice, allowing progressive infection with P. carinii. We found that CD4-depleted mice were unable to recruit CD4+ lymphocytes into their lungs and developed progressive infection with P. carinii, but mounted exuberant inflammatory responses to the organisms. These inflammatory responses were characterized by perivascular infiltration with mononuclear cells, increases in cell numbers in bronchoalveolar lavage (particularly CD8+ lymphocytes), and activation of alveolar macrophages (enhanced Ia antigen expression). In contrast, normal mice recruited CD4+ lymphocytes into their lungs and eliminated organisms with only minimal inflammatory responses. We conclude that depletion of CD4+ lymphocytes does not prevent the recruitment and activation of inflammatory cells in the lung. These inflammatory responses occur by mechanisms independent of CD4+ lymphocytes and are insufficient to provide effective host defense against P. carinii.
卡氏肺孢子菌是获得性免疫缺陷综合征患者最重要的肺部病原体，但宿主对卡氏肺孢子菌的防御机制尚未完全明确。我们最近报道了一种卡氏肺孢子菌感染的实验模型，在该模型中，选择性缺失CD4+淋巴细胞的小鼠接种卡氏肺孢子菌后会发生肺部感染。在本研究中，我们比较了CD4缺失小鼠和正常小鼠对卡氏肺孢子菌接种的肺部炎症反应，以进一步明确宿主对卡氏肺孢子菌的防御机制。我们假设，CD4+淋巴细胞的缺失会阻止这些小鼠肺部炎症细胞的募集和激活，从而使卡氏肺孢子菌得以进行性感染。我们发现，CD4缺失小鼠无法将CD4+淋巴细胞募集到肺部，并发生了卡氏肺孢子菌的进行性感染，但对该病原体产生了旺盛的炎症反应。这些炎症反应的特征包括单核细胞血管周围浸润、支气管肺泡灌洗中细胞数量增加（尤其是CD8+淋巴细胞）以及肺泡巨噬细胞激活（Ia抗原表达增强）。相比之下，正常小鼠将CD4+淋巴细胞募集到肺部，并仅以最小的炎症反应清除病原体。我们得出结论，CD4+淋巴细胞的缺失并不能阻止肺部炎症细胞的募集和激活。这些炎症反应通过独立于CD4+淋巴细胞的机制发生，且不足以提供有效的宿主防御以对抗卡氏肺孢子菌。
