4.6 Article

CD40-Activated B Cells Can Efficiently Prime Antigen-Specific Naive CD8+ T Cells to Generate Effector but Not Memory T cells

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PLOS ONE
卷 7, 期 1, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0030139

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资金

  1. Canadian Institutes of Health Research (CIHR) [MOP-77545, MOP-115139]
  2. Fonds de la recherche en sante du Quebec (FRSQ)
  3. Natural Sciences and Engineering Research Council of Canada

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Background: The identification of the signals that should be provided by antigen-presenting cells (APCs) to induce a CD8(+) T cell response in vivo is essential to improve vaccination strategies using antigen-loaded APCs. Although dendritic cells have been extensively studied, the ability of other APC types, such as B cells, to induce a CD8(+) T cell response have not been thoroughly evaluated. Methodology/Principal Findings: In this manuscript, we have characterized the ability of CD40-activated B cells, stimulated or not with Toll-like receptor (TLR) agonists (CpG or lipopolysaccharide) to induce the response of mouse naive CD8(+) T cells in vivo. Our results show that CD40-activated B cells can directly present antigen to naive CD8(+) T cells to induce the generation of potent effectors able to secrete cytokines, kill target cells and control a Listeria monocytogenes infection. However, CD40-activated B cell immunization did not lead to the proper formation of CD8(+) memory T cells and further maturation of CD40-activated B cells with TLR agonists did not promote the development of CD8(+) memory T cells. Our results also suggest that inefficient generation of CD8(+) memory T cells with CD40-activated B cell immunization is a consequence of reduced Bcl-6 expression by effectors and enhanced contraction of the CD8(+) T cell response. Conclusions: Understanding why CD40-activated B cell immunization is defective for the generation of memory T cells and gaining new insights about signals that should be provided by APCs are key steps before translating the use of CD40-B cell for therapeutic vaccination.

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