Dendritic cells ameliorate autoimmunity in the CNS by controlling the homeostasis of PD-1 receptor(+) regulatory T cells

Immunity. 2012 Aug 24;37(2):264-75. doi: 10.1016/j.immuni.2012.05.025. Epub 2012 Aug 16.


Mature dendritic cells (DCs) are established as unrivaled antigen-presenting cells (APCs) in the initiation of immune responses, whereas steady-state DCs induce peripheral T cell tolerance. Using various genetic approaches, we depleted CD11c(+) DCs in mice and induced autoimmune CNS inflammation. Unexpectedly, mice lacking DCs developed aggravated disease compared to control mice. Furthermore, when we engineered DCs to present a CNS-associated autoantigen in an induced manner, we found robust tolerance that prevented disease, which coincided with an upregulation of the PD-1 receptor on antigen-specific T cells. Additionally, we showed that PD-1 was necessary for DC-mediated induction of regulatory T cells. Our results show that a reduction of DCs interferes with tolerance, resulting in a stronger inflammatory response, and that other APC populations could compensate for the loss of immunogenic APC function in DC-depleted mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Autoantigens / immunology
  • Autoimmunity / immunology
  • B7-H1 Antigen / immunology
  • B7-H1 Antigen / metabolism
  • CD11c Antigen
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Immune Tolerance / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Programmed Cell Death 1 Receptor / immunology*
  • Programmed Cell Death 1 Receptor / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th17 Cells / immunology
  • Th17 Cells / metabolism


  • Autoantigens
  • B7-H1 Antigen
  • CD11c Antigen
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor