Constitutive induction of intestinal Tc17 cells in the absence of hematopoietic cell-specific MHC class II expression

Authors

  • Stephen J. Rubino,

    Corresponding author
    1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
    • Full correspondence: Dr. Stephen E. Girardin, Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8

      Fax: +1-416-978-5959

      e-mail: stephen.girardin@utoronto.ca

      Additional correspondence: Dr. Stephen J. Rubino, Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8

      Fax: +1-416-978-5959

      e-mail: stephen.rubino@utoronto.ca

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  • Kaoru Geddes,

    1. Department of Immunology, University of Toronto, Toronto, Canada
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  • Joao G. Magalhaes,

    1. Department of Immunology, University of Toronto, Toronto, Canada
    Current affiliation:
    1. Institut Curie, Paris
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  • Catherine Streutker,

    1. Department of Laboratory Medicine, St. Michael's Hospital, Toronto, Canada
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  • Dana J. Philpott,

    1. Department of Immunology, University of Toronto, Toronto, Canada
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  • Stephen E. Girardin

    Corresponding author
    1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
    • Full correspondence: Dr. Stephen E. Girardin, Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8

      Fax: +1-416-978-5959

      e-mail: stephen.girardin@utoronto.ca

      Additional correspondence: Dr. Stephen J. Rubino, Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8

      Fax: +1-416-978-5959

      e-mail: stephen.rubino@utoronto.ca

    Search for more papers by this author

Abstract

The enteric pathogen Citrobacter rodentium induces a mucosal IL-17 response in CD4+ T helper (Th17) cells that is dependent on the Nod-like receptors Nod1 and Nod2. Here, we sought to determine whether this early Th17 response required antigen presentation by major histocompatibility complex class II (MHCII) for full induction. At early phases of C. rodentium infection, we observed that the intestinal mucosal Th17 response was fully blunted in irradiated mice reconstituted with MHCII-deficient (MHCII−/−→WT) hematopoietic cells. Surprisingly, we also observed a substantial increase in the relative frequency of IL-17+CD8+CD4TCR-β+ cells (Tc17 cells) and FOXP3+CD8+CD4TCR-β+ cells in the lamina propria and intraepithelial lymphocyte compartment of MHCII−/−→WT mice compared with that in WT→WT counterparts. Moreover, MHCII−/−→WT mice displayed increased susceptibility, increased bacterial translocation to deeper organs, and more severe colonic histopathology after infection with C. rodentium. Finally, a similar phenotype was observed in mice deficient for CIITA, a transcriptional regulator of MHCII expression. Together, these results indicate that MHCII is required to mount early mucosal Th17 responses to an enteric pathogen, and that MHCII regulates the induction of atypical CD8+ T-cell subsets, such as Tc17 cells and FOXP3+CD8+ cells, in vivo.

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