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重组单核细胞增生李斯特菌在CD8 T细胞记忆产生过程中B细胞的特定作用。

A specific role for B cells in the generation of CD8 T cell memory by recombinant Listeria monocytogenes.

作者信息

Shen Hao, Whitmire Jason K, Fan Xin, Shedlock Devon J, Kaech Susan M, Ahmed Rafi

机构信息

Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

出版信息

J Immunol. 2003 Feb 1;170(3):1443-51. doi: 10.4049/jimmunol.170.3.1443.

Abstract

In this study, we investigated whether B cells play a role in the induction and maintenance of CD8 T cell memory after immunization with an intracellular bacterium, Listeria monocytogenes. Our results show that B cells play a minimal role in the initial activation and Ag-driven expansion of CD8 T lymphocytes. However, absence of B cells results in increased death of activated CD8 T cells during the contraction phase, leading to a lower level of Ag-specific CD8 T cell memory. Once memory is established, B cells are no longer required for the long-term maintenance and rapid recall response of memory CD8 T cells. Increased contraction of Ag-specific CD8 T cells in B cell-deficient mice is not due to impaired CD4 T cell responses since priming of epitope-specific CD4 T cell responses is normal in B cell-deficient mice following L. monocytogenes infection. Furthermore, no exaggerated contraction of Ag-specific CD8 T cells is evident in CD4 knockout mice. Thus, B cells play a specific role in modulating the contraction of CD8 T cell responses following immunization. Elucidation of factors that regulate the death phase may allow us to manipulate this process to increase the level of immunological memory and thus, vaccine efficacy.

摘要

在本研究中,我们调查了B细胞在用细胞内细菌单核细胞增生李斯特菌免疫后,是否在CD8 T细胞记忆的诱导和维持中发挥作用。我们的结果表明,B细胞在CD8 T淋巴细胞的初始激活和抗原驱动的扩增中起最小作用。然而,B细胞的缺失导致激活的CD8 T细胞在收缩期死亡增加,导致抗原特异性CD8 T细胞记忆水平降低。一旦建立记忆,记忆性CD8 T细胞的长期维持和快速回忆反应不再需要B细胞。B细胞缺陷小鼠中抗原特异性CD8 T细胞收缩增加并非由于CD4 T细胞反应受损,因为在单核细胞增生李斯特菌感染后,B细胞缺陷小鼠中表位特异性CD4 T细胞反应的启动是正常的。此外,在CD4基因敲除小鼠中没有明显的抗原特异性CD8 T细胞过度收缩。因此,B细胞在免疫后调节CD8 T细胞反应的收缩中起特定作用。阐明调节死亡期的因素可能使我们能够操纵这一过程,以提高免疫记忆水平,从而提高疫苗效力。

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