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

Jo, Norihide Zhang, Rui Ueno, Hideki Yamamoto, Takuya Weiskopf, Daniela Nagao, Miki Yamanaka, Shinya Hamazaki, Yoko 京都大学 DOI:10.3389/fragi.2021.719342

2021

概要

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.

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