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清除小鼠肺孢子菌感染时,CD4+ T细胞早期启动阶段需要B淋巴细胞。

B Lymphocytes Are Required during the Early Priming of CD4+ T Cells for Clearance of Pneumocystis Infection in Mice.

作者信息

Opata Michael M, Hollifield Melissa L, Lund Frances E, Randall Troy D, Dunn Robert, Garvy Beth A, Feola David J

机构信息

Division of Infectious Diseases, Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536;

Department of Microbiology, The University of Alabama at Birmingham, Birmingham, AL 35294;

出版信息

J Immunol. 2015 Jul 15;195(2):611-20. doi: 10.4049/jimmunol.1500112. Epub 2015 Jun 3.

Abstract

B cells play a critical role in the clearance of Pneumocystis. In addition to production of Pneumocystis-specific Abs, B cells are required during the priming phase for CD4(+) T cells to expand normally and generate memory. Clearance of Pneumocystis was found to be dependent on Ag specific B cells and on the ability of B cells to secrete Pneumocystis-specific Ab, as mice with B cells defective in these functions or with a restricted BCR were unable to control Pneumocystis infection. Because Pneumocystis-specific antiserum was only able to partially protect B cell-deficient mice from infection, we hypothesized that optimal T cell priming requires fully functional B cells. Using adoptive transfer and B cell depletion strategies, we determined that optimal priming of CD4(+) T cells requires B cells during the first 2-3 d of infection and that this was independent of the production of Ab. T cells that were removed from Pneumocystis-infected mice during the priming phase were fully functional and able to clear Pneumocystis infection upon adoptive transfer into Rag1(-/-) hosts, but this effect was ablated in mice that lacked fully functional B cells. Our results indicate that T cell priming requires a complete environment of Ag presentation and activation signals to become fully functional in this model of Pneumocystis infection.

摘要

B细胞在清除肺孢子菌中起关键作用。除了产生肺孢子菌特异性抗体外,在初始阶段B细胞是CD4(+) T细胞正常扩增并产生记忆所必需的。已发现肺孢子菌的清除依赖于抗原特异性B细胞以及B细胞分泌肺孢子菌特异性抗体的能力,因为在这些功能上有缺陷或BCR受限的B细胞的小鼠无法控制肺孢子菌感染。由于肺孢子菌特异性抗血清只能部分保护B细胞缺陷小鼠免受感染,我们推测最佳的T细胞初始需要功能完全正常的B细胞。使用过继转移和B细胞清除策略,我们确定CD4(+) T细胞的最佳初始在感染的前2 - 3天需要B细胞,并且这与抗体的产生无关。在初始阶段从感染肺孢子菌的小鼠中去除的T细胞功能完全正常,并且在过继转移到Rag1(-/-)宿主后能够清除肺孢子菌感染,但在缺乏功能完全正常的B细胞的小鼠中这种效应消失。我们的结果表明,在这种肺孢子菌感染模型中,T细胞初始需要完整的抗原呈递和激活信号环境才能完全发挥功能。

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