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Cell Rep. 2015 Jun 30;11(12):1929-40. doi: 10.1016/j.celrep.2015.05.042. Epub 2015 Jun 18.

CD8α(-) Dendritic Cells Induce Antigen-Specific T Follicular Helper Cells Generating Efficient Humoral Immune Responses.

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School of Life Sciences, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 689-798, Republic of Korea.
Laboratory of Cellular Physiology and Immunology and Chris Browne Center, The Rockefeller University, New York, NY 10065, USA.
Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-338, Republic of Korea.
Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Chonan-Si, Chungcheongnam-do 336-745, Republic of Korea. Electronic address:


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 CD8α(+) and CD8α(-) DC subsets. We show that CD8α(-) 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-κB signaling pathway. Tfh cells induced by CD8α(-) 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 CD8α(-) DCs in the initiation of Tfh cell differentiation and thereby provide a rationale for investigating CD8α(-) DCs in enhancing antigen-specific humoral immune responses for improving vaccines and therapeutics.

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