Alveolar macrophages instruct CD8+ T cell expansion by antigen cross-presentation in lung

Takumi Kawasaki; Moe Ikegawa; Kosuke Yunoki; Hifumi Otani; Daisuke Ori; Ken J Ishii; Etsushi Kuroda; Shiki Takamura; Masahiro Kitabatake; Toshihiro Ito; Ayako Isotani; Taro Kawai

doi:10.1016/j.celrep.2022.111828

Alveolar macrophages instruct CD8⁺ T cell expansion by antigen cross-presentation in lung

Cell Rep. 2022 Dec 13;41(11):111828. doi: 10.1016/j.celrep.2022.111828.

Authors

Affiliations

¹ Laboratory of Molecular Immunobiology, Nara Institute of Science and Technology (NAIST), Ikoma 630-0192, Japan. Electronic address: kawast01@bs.naist.jp.
² Laboratory of Molecular Immunobiology, Nara Institute of Science and Technology (NAIST), Ikoma 630-0192, Japan.
³ Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
⁴ Department of Immunology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
⁵ Department of Immunology, Faculty of Medicine, Kindai University, Osaka-Sayama 589-8511, Japan; Laboratory for Immunological Memory, Research Center for Integrative Medical Science (IMS), RIKEN Yokohama Institute, Yokohama 230-0045, Japan.
⁶ Department of Immunology, Nara Medical University, Kashihara 634-8521, Japan.
⁷ Organ Developmental Engineering, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology (NAIST), Ikoma 630-0192, Japan.
⁸ Laboratory of Molecular Immunobiology, Nara Institute of Science and Technology (NAIST), Ikoma 630-0192, Japan. Electronic address: tarokawai@bs.naist.jp.

PMID: 36516765
DOI: 10.1016/j.celrep.2022.111828

Abstract

Lung CD8⁺ memory T cells play central roles in protective immunity to respiratory viruses, such as influenza A virus (IAV). Here, we find that alveolar macrophages (AMs) function as antigen-presenting cells that support the expansion of lung CD8⁺ memory T cells. Intranasal antigen administration to mice subcutaneously immunized with antigen results in a rapid expansion of antigen-specific CD8⁺ T cells in the lung, which is dependent on antigen cross-presentation by AMs. AMs highly express interleukin-18 (IL-18), which mediates subsequent formation of CD103⁺CD8⁺ resident memory T (T_RM) cells in the lung. In a mouse model of IAV infection, AMs are required for expansion of virus-specific CD8⁺ T cells and CD103⁺CD8⁺ T_RM cells and inhibiting virus replication in the lungs during secondary infection. These results suggest that AMs instruct a rapid expansion of antigen-specific CD8⁺ T cells in lung, which protect the host from respiratory virus infection.

Keywords: CP: Immunology; IL-18; alveolar macrophage; antigen presentation; cross-presentation; dendritic cell; influenza A virus; resident memory CD8(+) T cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD8-Positive T-Lymphocytes
Cross-Priming
Immunologic Memory
Influenza A virus*
Lung
Macrophages, Alveolar
Mice
Orthomyxoviridae Infections*