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

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.