Aging and CMV Infection Affect Pre-existing SARS-CoV-2-Reactive CD8⁺ T Cells in Unexposed Individuals

DOI HANDLE Web Site 2 Citations 72 References Open Access
  • Jo, Norihide
    Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University; Alliance Laboratory for Advanced Medical Research, Graduate School of Medicine, Kyoto University
  • Zhang, Rui
    Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University
  • Ueno, Hideki
    Department of Immunology, Graduate School of Medicine, Kyoto University; Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University
  • Yamamoto, Takuya
    Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University; Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University
  • Weiskopf, Daniela
    Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology
  • Nagao, Miki
    Department of Clinical Laboratory Medicine, Graduate School of Medicine, Kyoto University
  • Yamanaka, Shinya
    Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University; Gladstone Institute of Cardiovascular Disease
  • Hamazaki, Yoko
    Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University; Laboratory of Immunobiology, Graduate School of Medicine, Kyoto University

Abstract

Age is a major risk factor for COVID-19 severity, and T cells play a central role in anti-SARS-CoV-2 immunity. Because SARS-CoV-2-cross-reactive T cells have been detected in unexposed individuals, we investigated the age-related differences in pre-existing SARS-CoV-2-reactive T cells. SARS-CoV-2-reactive CD4⁺ T cells from young and elderly individuals were mainly detected in the central memory fraction and exhibited similar functionalities and numbers. Naïve-phenotype SARS-CoV-2-reactive CD8⁺ T cell populations decreased markedly in the elderly, while those with terminally differentiated and senescent phenotypes increased. Furthermore, senescent SARS-CoV-2-reactive CD8⁺ T cell populations were higher in cytomegalovirus seropositive young individuals compared to seronegative ones. Our findings suggest that age-related differences in pre-existing SARS-CoV-2-reactive CD8+ T cells may explain the poor outcomes in elderly patients and that cytomegalovirus infection is a potential factor affecting CD8⁺ T cell immunity against SARS-CoV-2. Thus, this study provides insights for developing effective therapeutic and vaccination strategies for the elderly.

Severe COVID-19 symptoms in the elderly are consistent with a weaker immune system. 京都大学プレスリリース. 2021-08-23.

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