Allendörfer R, Brunner G D, Deepe G S
Division of Infectious Diseases, University of Cincinnati College of Medicine, OH 45267, USA.
J Immunol. 1999 Jun 15;162(12):7389-96.
The presence of functional T cells is often required for successful resolution of infections with intracellular pathogens, yet the mechanisms by which they contribute to elimination of the invading pathogen in primary and secondary immunity are only partly understood. We report that increased mortality of naive alpha/beta TCR+ or CD4+ T cell-depleted mice infected with the fungus Histoplasma capsulatum is associated with impairment of IFN-gamma production. Upon secondary infection, mice concomitantly depleted of CD4+ and CD8+ cells exhibit decreased survival beyond day 25 of rechallenge, whereas elimination of either T cell subset or B cell deficiency does not result in accelerated mortality compared with controls. Remarkably, despite a decrease of H. capsulatum CFU in lungs of CD4+ plus CD8+-deficient mice, a progressive increase in spleen CFU is observed. The ability to control fungus growth in lungs is associated with vigorous TNF-alpha, but not IFN-gamma, production by bronchoalveolar lavage cells. In contrast, spleen cells from CD4+ plus CD8+-deficient mice are unable to produce TNF-alpha. Thus, the cellular and molecular requirements for protective immunity vary between primary and secondary infection. Furthermore, in secondary histoplasmosis, a sharp contrast can be drawn between lungs and spleens in their reliance upon T cells to control fungal replication. The opposing activities of these organs can be ascribed in part to differential production of TNF-alpha.
功能性T细胞的存在通常是成功清除细胞内病原体感染所必需的，然而它们在初次免疫和二次免疫中促进清除入侵病原体的机制仅得到部分理解。我们报告，感染荚膜组织胞浆菌的初始α/β TCR⁺或CD4⁺ T细胞耗竭小鼠死亡率增加与IFN-γ产生受损有关。二次感染时，同时耗竭CD4⁺和CD8⁺细胞的小鼠在再次攻击后第25天之后存活率降低，而与对照组相比，消除任一T细胞亚群或B细胞缺陷均不会导致死亡率加速上升。值得注意的是，尽管CD4⁺加CD8⁺缺陷小鼠肺部的荚膜组织胞浆菌CFU减少，但脾脏CFU却出现逐渐增加。肺部控制真菌生长的能力与支气管肺泡灌洗细胞产生强烈的TNF-α有关，而与IFN-γ无关。相比之下，CD4⁺加CD8⁺缺陷小鼠的脾脏细胞无法产生TNF-α。因此，初次感染和二次感染之间保护性免疫的细胞和分子需求有所不同。此外，在二次组织胞浆菌病中，肺部和脾脏在依赖T细胞控制真菌复制方面形成鲜明对比。这些器官的相反活动部分可归因于TNF-α的差异产生。
