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

Immunol Lett. 2016 Apr:172:21-8. doi: 10.1016/j.imlet.2016.01.009. Epub 2016 Feb 2.

Abstract

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, CD8α(+) DCs or CD8α(-) DCs. Here we demonstrated that the localization of CD8α(-) 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 CD8α(-) DCs, and IL-6 directly secreted from the DC subsets seems minor. CD8α(-) 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 CD8α(-) DC subset as therapeutic vaccine for the regulation of humoral immune responses.

Keywords: Cellular immunity; Cytokine; Dendritic cell subset; Humoral immunity; Localization; T follicular helper cell.

MeSH terms

  • Animals
  • Antigen Presentation
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8 Antigens / metabolism
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation
  • Germinal Center / immunology
  • Immunity, Humoral
  • Immunotherapy, Adoptive / methods*
  • Interleukin-6 / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, CCR7 / metabolism
  • Receptors, CXCR5 / metabolism

Substances

  • CD8 Antigens
  • CD8alpha antigen
  • CXCR5 protein, mouse
  • Ccr7 protein, mouse
  • Interleukin-6
  • Receptors, CCR7
  • Receptors, CXCR5