Conditional ablation of CD205+ conventional dendritic cells impacts the regulation of T-cell immunity and homeostasis in vivo.
Dendritic cells (DCs) are composed of multiple subsets that play a dual role in inducing immunity and tolerance. However, it is unclear how CD205(+) conventional DCs (cDCs) control immune responses in vivo. Here we generated knock-in mice with the selective conditional ablation of CD205(+) cDCs. CD205(+) cDCs contributed to antigen-specific priming of CD4(+) T cells under steady-state conditions, whereas they were dispensable for antigen-specific CD4(+) T-cell responses under inflammatory conditions. In contrast, CD205(+) cDCs were required for antigen-specific priming of CD8(+) T cells to generate cytotoxic T lymphocytes (CTLs) mediated through cross-presentation. Although CD205(+) cDCs were involved in the thymic generation of CD4(+) regulatory T cells (Tregs), they maintained the homeostasis of CD4(+) Tregs and CD4(+) effector T cells in peripheral and mucosal tissues. On the other hand, CD205(+) cDCs were involved in the inflammation triggered by Toll-like receptor ligand as well as bacterial and viral infections. Upon microbial infections, CD205(+) cDCs contributed to the cross-priming of CD8(+) T cells for generating antimicrobial CTLs to efficiently eliminate pathogens, whereas they suppressed antimicrobial CD4(+) T-cell responses. Thus, these findings reveal a critical role for CD205(+) cDCs in the regulation of T-cell immunity and homeostasis in vivo.
Laboratory for Dendritic Cell Immunobiology, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Tomohiro
T
Fukaya
Ryuichi
R
Murakami
Hideaki
H
Takagi
Kaori
K
Sato
Yumiko
Y
Sato
Haruna
H
Otsuka
Michiko
M
Ohno
Atsushi
A
Hijikata
Osamu
O
Ohara
Masaki
M
Hikida
Bernard
B
Malissen
Katsuaki
K
Sato
D020413:3' Untranslated Regions; D056704:Adaptive Immunity; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007249:Inflammation; D037181:Lectins, C-Type / Q000096:biosynthesis* / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology*
D020413:3' Untranslated Regions; D015703:Antigens, CD; C093569:DEC-205 receptor; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D049452:Green Fluorescent Proteins