Jo et al. characterized cDC1 (Δ32 mice)- and cDC2 (Δ1+2+3 mice)-deficient mouse models and evaluated the role of DC subsets in the priming of CD4+ and CD8+ T cells in response to several forms of antigen in vivo. cDC1s were necessary and sufficient for the priming of both CD4+ and CD8+ T cells for cell-associated antigens, but dispensable for antigens derived from immune complex (IC) antigens. cDC2 were sufficient for cross-presentation of IC antigens in cDC1-deficient (Δ32 mice), leading to the induction of CD8+ T cell responses that protected against immunogenic tumors in a WDFY4-dependent manner.
Contributed by Shishir Pant
ABSTRACT: Priming CD8+ T cells against tumors or viral pathogens results largely from cross-presentation of exogenous antigens by type 1 conventional dendritic cells (cDC1s). Although monocyte-derived DCs and cDC2s can cross-present in vitro, their physiological relevance remains unclear. Here, we used genetic models to evaluate the role of cDC subsets in presentation of cell-associated and immune complex antigens to CD4+ and CD8+ T cells in vivo. For cell-associated antigens, cDC1s were necessary and sufficient to prime both CD4+ and CD8+ T cells. In contrast, for immune complex antigens, either cDC1 or cDC2, but not monocyte-derived DCs, could carry out cross-presentation to CD8+ T cells. Mice lacking cDC1 and vaccinated with immune complexes could cross-prime CD8+ T cells that were sufficient to mediate tumor rejection. Notably, this cross-presentation mediated by cDC2 was also WDFY4 dependent, similar to cross-presentation of cell-associated antigens by cDC1. These results demonstrate a previously unrecognized activity of WDFY4 in cDC2s and suggest a cross-presentation pathway shared by cDC subsets.
Author Info: (1) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 (2) Department of Pathology an
Author Info: (1) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 (2) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 (3) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 (4) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 (5) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 (6) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 (7) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 (8) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 (9) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 (10) Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 Siteman Cancer Center, Washington University School of Medicine , St. Louis, MO, USA. ROR: https://ror.org/04cf69335 (11) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 (12) Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University in St. Louis, School of Medicine , St. Louis, MO, USA. ROR: https://ror.org/04cf69335 (13) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University in St. Louis, School of Medicine , St. Louis, MO, USA. ROR: https://ror.org/04cf69335 Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 (14) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335 (15) Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. ROR: https://ror.org/04cf69335
