Intrinsic features of the CD8α- dendritic cell subset in inducing functional T follicular helper cells

T follicular helper (Tfh) cells, a true B cell helper, have a critical role in enhancing humoral immune responses. However, the initial differentiation of Tfh cells by dendritic cells (DCs), the most potent antigen presenting cells, has not been clearly understood, particularly in the knowledge of the two major conventional dendritic cell subsets, CD8 alpha(+) DCs or CD8 alpha(-) DCs. Here we demonstrated that the localization of CD8 alpha(-) DCs in the marginal zone (MZ) bridging channels is closely associated with the induction of CXCR5(+)CCR7(low) Tfh cells. We also showed that the major source of IL-6 for inducing Tfh cells is provided from the activated CD4(+) T cells induced by CD8 alpha(-) DCs, and IL-6 directly secreted from the DC subsets seems minor. CD8 alpha(-) DCs were superior in inducing functional Tfh cells over other antigen presenting cells including B cells. We here observed the unknown intrinsic features of the DC subsets, suggesting the potential of utilizing the CD8 alpha(-) DC subset as therapeutic vaccine for the regulation of humoral immune responses. (C) 2016 The Authors. Published by Elsevier B.V. on behalf of European Federation of Immunological Societies. This is an open access article under the CC BY-NC-ND license.