Helminth Antigen-Conditioned Dendritic Cells Generate Anti-Inflammatory Cd4 T Cells Independent of Antigen Presentation via Major Histocompatibility Complex Class II

Am J Pathol. 2018 Nov;188(11):2589-2604. doi: 10.1016/j.ajpath.2018.07.008. Epub 2018 Aug 17.


A recently identified feature of the host response to infection with helminth parasites is suppression of concomitant disease. Dendritic cells (DCs) exposed to antigens from the tapeworm Hymenolepis diminuta significantly reduce the severity of dinitrobenzene sulfonic acid-induced colitis in mice. Here we elucidate mechanisms underlying this cellular immunotherapy. We show a requirement for Ccr7 expression on transferred H. diminuta antigen-treated (HD)-DCs, suggesting that homing to secondary lymphoid tissues is important for suppression of colitis. Furthermore, sodium metaperiodate-sensitive helminth-derived glycans are required to drive the anti-colitic response in recipient mice. Induction of Th2-type cytokines and Gata-3+Cd4+ cells in secondary lymphoid tissues is dependent on major histocompatibility complex class II (MHC II) protein expression on transferred DCs, although remarkably, transfer of MHC II-/- HD-DCs still attenuated dinitrobenzene sulfonic acid-induced colitis in recipient mice. Moreover, transfer of Cd4+ splenic T cells retrieved from mice administered MHC II-/- HD-DCs suppressed dinitrobenzene sulfonic acid-induced colitis in recipient mice. Our studies reveal that HD-DCs can suppress colitis via an alternative MHC II-independent pathway that involves, in part, mobilization of T-cell responses. These data support the utility of HD-DCs in blocking colitis, revealing a requirement for Ccr7 and providing for HD-DC autologous immunotherapy for disease in which MHC II expression and/or function is compromised.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antigen Presentation / immunology*
  • Antigens, Helminth / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Colitis / chemically induced
  • Colitis / immunology
  • Colitis / prevention & control*
  • Cytokines
  • Dendritic Cells / immunology*
  • Histocompatibility Antigens Class II / physiology*
  • Hymenolepis diminuta / immunology
  • Immunotherapy
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout


  • Anti-Inflammatory Agents
  • Antigens, Helminth
  • Cytokines
  • Histocompatibility Antigens Class II