High levels of soluble CD25 in COVID‐19 severity suggest a divergence between anti‐viral and pro‐inflammatory T‐cell responses
Abstract Objectives We aimed to gain an understanding of the paradox of the immunity in COVID‐19 patients with T cells showing both functional defects and hyperactivation and enhanced proliferation. Methods A total of 280 hospitalised patients with COVID‐19 were evaluated for cytokine profiles and c...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Clinical & Translational Immunology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cti2.1251 |
| _version_ | 1818439553132789760 |
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| author | Min Xie Joseph Yunis Yin Yao Jing Shi Yang Yang Pengcheng Zhou Kaili Liang Yanmin Wan Ahmed Mehdi Zhian Chen Naiqi Wang Shuyun Xu Min Zhou Muqing Yu Ke Wang Yu Tao Ying Zhou Xiaochen Li Xiansheng Liu Xiao Yu Yunbo Wei Zheng Liu Jonathan Sprent Di Yu |
| author_facet | Min Xie Joseph Yunis Yin Yao Jing Shi Yang Yang Pengcheng Zhou Kaili Liang Yanmin Wan Ahmed Mehdi Zhian Chen Naiqi Wang Shuyun Xu Min Zhou Muqing Yu Ke Wang Yu Tao Ying Zhou Xiaochen Li Xiansheng Liu Xiao Yu Yunbo Wei Zheng Liu Jonathan Sprent Di Yu |
| author_sort | Min Xie |
| collection | DOAJ |
| description | Abstract Objectives We aimed to gain an understanding of the paradox of the immunity in COVID‐19 patients with T cells showing both functional defects and hyperactivation and enhanced proliferation. Methods A total of 280 hospitalised patients with COVID‐19 were evaluated for cytokine profiles and clinical features including viral shedding. A mouse model of acute infection by lymphocytic choriomeningitis virus (LCMV) was applied to dissect the relationship between immunological, virological and pathological features. The results from the mouse model were validated by published data set of single‐cell RNA sequencing (scRNA‐seq) of immune cells in bronchoalveolar lavage fluid (BALF) of COVID‐19 patients. Results The levels of soluble CD25 (sCD25), IL‐6, IL‐8, IL‐10 and TNF‐α were higher in severe COVID‐19 patients than non‐severe cases, but only sCD25 was identified as an independent risk factor for disease severity by multivariable binary logistic regression analysis and showed a positive association with the duration of viral shedding. In agreement with the clinical observation, LCMV‐infected mice with high levels of sCD25 demonstrated insufficient anti‐viral response and delayed viral clearance. The elevation of sCD25 in mice was mainly contributed by the expansion of CD25+CD8+ T cells that also expressed the highest level of PD‐1 with pro‐inflammatory potential. The counterpart human CD25+PD‐1+ T cells were expanded in BALF of COVID‐19 patients with severe disease compared to those with modest disease. Conclusion These results suggest that high levels of sCD25 in COVID‐19 patients probably result from insufficient anti‐viral immunity and indicate an expansion of pro‐inflammatory T cells that contribute to disease severity. |
| first_indexed | 2024-12-14T17:58:17Z |
| format | Article |
| id | doaj.art-549c1a664b374a3c8d00bbcd8de9b94f |
| institution | Directory Open Access Journal |
| issn | 2050-0068 |
| language | English |
| last_indexed | 2024-12-14T17:58:17Z |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical & Translational Immunology |
| spelling | doaj.art-549c1a664b374a3c8d00bbcd8de9b94f2022-12-21T22:52:30ZengWileyClinical & Translational Immunology2050-00682021-01-01102n/an/a10.1002/cti2.1251High levels of soluble CD25 in COVID‐19 severity suggest a divergence between anti‐viral and pro‐inflammatory T‐cell responsesMin Xie0Joseph Yunis1Yin Yao2Jing Shi3Yang Yang4Pengcheng Zhou5Kaili Liang6Yanmin Wan7Ahmed Mehdi8Zhian Chen9Naiqi Wang10Shuyun Xu11Min Zhou12Muqing Yu13Ke Wang14Yu Tao15Ying Zhou16Xiaochen Li17Xiansheng Liu18Xiao Yu19Yunbo Wei20Zheng Liu21Jonathan Sprent22Di Yu23Department of Respiratory and Critical Care Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaThe University of Queensland Diamantina Institute Faculty of Medicine The University of Queensland Brisbane QLD AustraliaThe University of Queensland Diamantina Institute Faculty of Medicine The University of Queensland Brisbane QLD AustraliaDepartment of Respiratory and Critical Care Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaThe University of Queensland Diamantina Institute Faculty of Medicine The University of Queensland Brisbane QLD AustraliaThe University of Queensland Diamantina Institute Faculty of Medicine The University of Queensland Brisbane QLD AustraliaChina–Australia Centre for Personalised Immunology Shanghai Renji Hospital Shanghai Jiaotong University School of Medicine ShanghaiDepartment of Infectious Diseases Huashan Hospital Fudan University Shanghai ChinaThe University of Queensland Diamantina Institute Faculty of Medicine The University of Queensland Brisbane QLD AustraliaThe University of Queensland Diamantina Institute Faculty of Medicine The University of Queensland Brisbane QLD AustraliaThe University of Queensland Diamantina Institute Faculty of Medicine The University of Queensland Brisbane QLD AustraliaDepartment of Respiratory and Critical Care Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Respiratory and Critical Care Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Respiratory and Critical Care Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Respiratory and Critical Care Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Respiratory and Critical Care Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Respiratory and Critical Care Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Respiratory and Critical Care Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Respiratory and Critical Care Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaShandong Artificial Intelligence Institute Qilu University of Technology (Shandong Academy of Sciences) Jinan ChinaDepartment of Otolaryngology‐Head and Neck Surgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaImmunology Division Garvan Institute of Medical Research Darlinghurst NSW AustraliaThe University of Queensland Diamantina Institute Faculty of Medicine The University of Queensland Brisbane QLD AustraliaAbstract Objectives We aimed to gain an understanding of the paradox of the immunity in COVID‐19 patients with T cells showing both functional defects and hyperactivation and enhanced proliferation. Methods A total of 280 hospitalised patients with COVID‐19 were evaluated for cytokine profiles and clinical features including viral shedding. A mouse model of acute infection by lymphocytic choriomeningitis virus (LCMV) was applied to dissect the relationship between immunological, virological and pathological features. The results from the mouse model were validated by published data set of single‐cell RNA sequencing (scRNA‐seq) of immune cells in bronchoalveolar lavage fluid (BALF) of COVID‐19 patients. Results The levels of soluble CD25 (sCD25), IL‐6, IL‐8, IL‐10 and TNF‐α were higher in severe COVID‐19 patients than non‐severe cases, but only sCD25 was identified as an independent risk factor for disease severity by multivariable binary logistic regression analysis and showed a positive association with the duration of viral shedding. In agreement with the clinical observation, LCMV‐infected mice with high levels of sCD25 demonstrated insufficient anti‐viral response and delayed viral clearance. The elevation of sCD25 in mice was mainly contributed by the expansion of CD25+CD8+ T cells that also expressed the highest level of PD‐1 with pro‐inflammatory potential. The counterpart human CD25+PD‐1+ T cells were expanded in BALF of COVID‐19 patients with severe disease compared to those with modest disease. Conclusion These results suggest that high levels of sCD25 in COVID‐19 patients probably result from insufficient anti‐viral immunity and indicate an expansion of pro‐inflammatory T cells that contribute to disease severity.https://doi.org/10.1002/cti2.1251CD25+PD‐1+ CD8+ T cellCOVID‐19 patientsdisease severitySARS‐CoV‐2soluble CD25 |
| spellingShingle | Min Xie Joseph Yunis Yin Yao Jing Shi Yang Yang Pengcheng Zhou Kaili Liang Yanmin Wan Ahmed Mehdi Zhian Chen Naiqi Wang Shuyun Xu Min Zhou Muqing Yu Ke Wang Yu Tao Ying Zhou Xiaochen Li Xiansheng Liu Xiao Yu Yunbo Wei Zheng Liu Jonathan Sprent Di Yu High levels of soluble CD25 in COVID‐19 severity suggest a divergence between anti‐viral and pro‐inflammatory T‐cell responses Clinical & Translational Immunology CD25+PD‐1+ CD8+ T cell COVID‐19 patients disease severity SARS‐CoV‐2 soluble CD25 |
| title | High levels of soluble CD25 in COVID‐19 severity suggest a divergence between anti‐viral and pro‐inflammatory T‐cell responses |
| title_full | High levels of soluble CD25 in COVID‐19 severity suggest a divergence between anti‐viral and pro‐inflammatory T‐cell responses |
| title_fullStr | High levels of soluble CD25 in COVID‐19 severity suggest a divergence between anti‐viral and pro‐inflammatory T‐cell responses |
| title_full_unstemmed | High levels of soluble CD25 in COVID‐19 severity suggest a divergence between anti‐viral and pro‐inflammatory T‐cell responses |
| title_short | High levels of soluble CD25 in COVID‐19 severity suggest a divergence between anti‐viral and pro‐inflammatory T‐cell responses |
| title_sort | high levels of soluble cd25 in covid 19 severity suggest a divergence between anti viral and pro inflammatory t cell responses |
| topic | CD25+PD‐1+ CD8+ T cell COVID‐19 patients disease severity SARS‐CoV‐2 soluble CD25 |
| url | https://doi.org/10.1002/cti2.1251 |
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