Conditional ablation of CD205+ conventional dendritic cells impacts the regulation of T-cell immunity and homeostasis in vivo.

Abstract

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.

• Authors: Tomohiro Fukaya, Ryuichi Murakami, Hideaki Takagi, Kaori Sato, Yumiko Sato, Haruna Otsuka, Michiko Ohno, Atsushi Hijikata, Osamu Ohara, Masaki Hikida, Bernard Malissen, Katsuaki Sato
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 109 Issue 28 Pg. 11288-93 (Jul 10 2012) ISSN: 1091-6490 [Electronic] United States
• PMID: 22736794 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3' Untranslated Regions
• Antigens, CD
• DEC-205 receptor
• Lectins, C-Type
• Minor Histocompatibility Antigens
• Receptors, Cell Surface
• Green Fluorescent Proteins

Topics

• 3' Untranslated Regions
• Adaptive Immunity
• Animals
• Antigens, CD (biosynthesis, chemistry)
• CD4-Positive T-Lymphocytes (immunology)
• Cross-Priming (immunology)
• Dendritic Cells (cytology)
• Green Fluorescent Proteins (metabolism)
• Homeostasis
• Humans
• Immune Tolerance (immunology)
• Inflammation
• Lectins, C-Type (biosynthesis, chemistry)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Minor Histocompatibility Antigens
• Receptors, Cell Surface (biosynthesis, chemistry)
• T-Lymphocytes (immunology)