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PLoS One. 2012;7(1):e30139. doi: 10.1371/journal.pone.0030139. Epub 2012 Jan 23.

CD40-activated B cells can efficiently prime antigen-specific naïve CD8+ T cells to generate effector but not memory T cells.

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1
Maisonneuve-Rosemont Hospital Research Center, Montréal, Québec, Canada.

Abstract

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 naïve CD8(+) T cells in vivo. Our results show that CD40-activated B cells can directly present antigen to naïve 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.

PMID:
22291907
PMCID:
PMC3264565
DOI:
10.1371/journal.pone.0030139
[Indexed for MEDLINE]
Free PMC Article
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