Aging Inhibits Memory Immune Response of CD8+T Cells in Lungs of C57BL/6J Mice Against Influenza A(H1N1)Virus
10.12300/j.issn.1674-5817.2025.066
- VernacularTitle:衰老抑制C57BL/6J小鼠肺部CD8+T细胞对甲型H1N1流感病毒的记忆性免疫应答
- Author:
Chao WANG
1
;
Shun LI
1
;
Xiaonan REN
1
;
Hua YANG
1
;
Lixiang CHEN
1
;
Chunhua XU
1
;
Xiaohui ZHOU
1
Author Information
1. 复旦大学附属公共卫生临床中心,上海 201508
- Publication Type:Journal Article
- Keywords:
Influenza A(H1N1)virus;
CD8+T cells;
Immunosenescence;
Memory immune response;
Mice
- From:
Laboratory Animal and Comparative Medicine
2025;45(5):515-523
- CountryChina
- Language:Chinese
-
Abstract:
Objective To compare functional differences of CD8+T cells in lung tissues between young and aged C57BL/6J mice during the contraction phase and memory immune response phase after infection with influenza A(H1N1)virus.Methods Lung tissues from young(3-month-old)and aged(24-month-old)C57BL/6J female mice without influenza virus infection were collected to prepare single-cell suspensions,which were stimulated with phorbol 12-myristate 13-acetate(PMA)/ionomycin or cluster of differentiation(CD)3/CD28 antibodies(T-cell antigen receptor/co-stimulatory signals)respectively(non-specific antigens stimulation).Flow cytometry intracellular cytokine staining(ICS)was performed on lung CD8+T cells to detect their secretion capacity of tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ).Young and aged C57BL/6J mice were infected intranasally with 490 PFU PR8 influenza virus,and reinfected with homologous influenza virus 28 days later.Lung tissues were isolated on day 28(the contraction phase)and day 32(the memory immune response phase)after primary infection.Influenza virus-specific MHC-Ⅰ tetramer staining was used to detect the proportion of virus-specific CD8+T cells in lung tissue CD8+T cells,and ICS was used to analyze TNF-α,IFN-γ,and granzyme B expression in CD8+CD44high T cell subset.Results After non-specific antigen stimulation,TNF-α and IFN-γ secretion capacity in lung tissue CD8+T cells of aged group mice was significantly higher than that of young group(P＜0.05).After virus-specific antigen stimulation,there were no statistically significant differences in the proportion of virus-specific CD8+T cells and the expression levels of TNF-α,IFN-γ,and granzyme B between the two groups of mice during the contraction phase(P＞0.05),while during the memory immune response phase,the proportion of virus-specific CD8+T cells and the expression levels of TNF-α,IFN-γ,and granzyme B in the aged group mice were significantly lower than those in the young group(P＜0.05).Conclusion CD8+T cells in aged mice maintain normal immune-related factor expression function under non-specific antigen stimulation,but show impaired immune-related factor expression function during antigen-specific memory immune response phase,suggesting that aging leads to defects in the formation or maintenance of CD8+T cell immune memory.
