title: Constitutive induction of intestinal Tc17 cells in the absence of hematopoietic cell-specific MHC class II expression.
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(+) CD4(-) TCR-β(+) cells (Tc17 cells) and FOXP3(+) CD8(+) CD4(-) TCR-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.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rubino
authors.forename: Kaoru
authors.initials: K
authors.lastname: Geddes
authors.forename: Joao G
authors.initials: JG
authors.lastname: Magalhaes
authors.forename: Catherine
authors.initials: C
authors.lastname: Streutker
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Philpott
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Girardin
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D044082:Citrobacter rodentium / Q000276:immunology*; D004756:Enterobacteriaceae Infections / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005802:Genes, MHC Class II / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000378:metabolism; D007422:Intestines / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000949:Histocompatibility Antigens Class II; D020381:Interleukin-17; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015534:Trans-Activators
keywords: Citrobacter rodentium; FOXP3+CD8+; IL-17; MHC class II; Tc17