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

• Published in: Frontiers in aging Vol. 2; p. 719342
• Main Authors: Jo, Norihide, Zhang, Rui, Ueno, Hideki, Yamamoto, Takuya, Weiskopf, Daniela, Nagao, Miki, Yamanaka, Shinya, Hamazaki, Yoko
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 2021
• Subjects: Aging; COVID-19; cross-reactive T cells; cytomegalovirus; SARS-CoV-2; senescent T cells; T-cell immunity
• ISSN: 2673-6217; 2673-6217
• DOI: 10.3389/fragi.2021.719342

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.