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CD8 alpha(-) Dendritic Cells Induce Antigen-Specific T Follicular Helper Cells Generating Efficient Humoral Immune Responses

Author(s)
Shin, ChangsikHan, Jae-AKoh, HyeinChoi, BongseoCho, YongbinJeong, HyeongminRa, Jea-SunSung, Pil SooShin, Eui-CheolRyu, SeonghoDo, Yoonkyung
Issued Date
2015-06
DOI
10.1016/j.celrep.2015.05.042
URI
https://scholarworks.unist.ac.kr/handle/201301/17009
Fulltext
http://www.sciencedirect.com/science/article/pii/S2211124715005781
Citation
CELL REPORTS, v.11, no.12, pp.1929 - 1940
Abstract
Recent studies on T follicular helper (Tfh) cells have significantly advanced our understanding of T cell-dependent B cell responses. However, little is known about the early stage of Tfh cell commitment by dendritic cells (DCs), particularly by the conventional CD8 alpha(+) and CD8 alpha(-) DC subsets. We show that CD8 alpha(-) DCs localized at the interfollicular zone play a pivotal role in the induction of antigen-specific Tfh cells by upregulating the expression of Icosl and Ox40l through the non-canonical NF-kappa B signaling pathway. Tfh cells induced by CD8 alpha(-) DCs function as true B cell helpers, resulting in significantly increased humoral immune responses against various human pathogenic antigens, including Yersinia pestis LcrV, HIV Gag, and hepatitis B surface antigen. Our findings uncover a mechanistic role of CD8 alpha(-) DCs in the initiation of Tfh cell differentiation and thereby provide a rationale for investigating CD8 alpha(-) DCs in enhancing antigen-specific humoral immune responses for improving vaccines and therapeutics
Publisher
Cell Press
ISSN
2211-1247
Keyword
CXC CHEMOKINE RECEPTOR-5HEPATITIS-B-VACCINEIN-VIVOANTIBODY-PRODUCTIONHIV-INFECTIONDIFFERENTIATIONEXPRESSIONMOUSEICOSFOLLICLES

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