Characterization of age-related immune features after autologous NK cell infusion: Protocol for an open-label and randomized controlled trial
BackgroundAging is usually accompanied by functional declines of the immune system, especially in T-cell responses. However, little is known about ways to alleviate this.MethodsHere, 37 middle-aged healthy participants were recruited, among which 32 were intravenously administrated with expanded NK...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.940577/full |
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| author | Xiaofeng Tang Biaolong Deng Aiping Zang Xiaowen He Ye Zhou Daimeng Wang Dan Li Xueyu Dai Jieqiong Chen Xuhua Zhang Ye Liu Yonghua Xu Jingjing Chen Weijie Zheng Luding Zhang Constance Gao Huanfeng Yang Bin Li Xueqi Wang |
| author_facet | Xiaofeng Tang Biaolong Deng Aiping Zang Xiaowen He Ye Zhou Daimeng Wang Dan Li Xueyu Dai Jieqiong Chen Xuhua Zhang Ye Liu Yonghua Xu Jingjing Chen Weijie Zheng Luding Zhang Constance Gao Huanfeng Yang Bin Li Xueqi Wang |
| author_sort | Xiaofeng Tang |
| collection | DOAJ |
| description | BackgroundAging is usually accompanied by functional declines of the immune system, especially in T-cell responses. However, little is known about ways to alleviate this.MethodsHere, 37 middle-aged healthy participants were recruited, among which 32 were intravenously administrated with expanded NK cells and 5 with normal saline. Then, we monitored changes of peripheral senescent and exhausted T cells within 4 weeks after infusion by flow cytometry, as well as serum levels of senescence-associated secretory phenotype (SASP)-related factors. In vitro co-culture assays were performed to study NK-mediated cytotoxic activity against senescent or exhausted T cells. Functional and phenotypic alteration of NK cells before and after expansion was finally characterized.ResultsAfter NK cell infusion, senescent CD28-, CD57+, CD28-CD57+, and CD28-KLRG1+ CD4+ and CD8+ T-cell populations decreased significantly, so did PD-1+ and TIM-3+ T cells. These changes were continuously observed for 4 weeks. Nevertheless, no significant changes were observed in the normal saline group. Moreover, SASP-related factors including IL-6, IL-8, IL-1α, IL-17, MIP-1α, MIP-1β, and MMP1 were significantly decreased after NK cell infusion. Further co-culture assays showed that expanded NK cells specifically and dramatically eliminated senescent CD4+ T cells other than CD28+CD4+ T cells. They also showed improved cytotoxic activity, with different expression patterns of activating and inhibitory receptors including NKG2C, NKG2A, KLRG1, LAG3, CD57, and TIM3.ConclusionOur findings imply that T-cell senescence and exhaustion is a reversible process in healthy individuals, and autologous NK cell administration can be introduced to alleviate the aging.Clinical Trial RegistrationClinicalTrials.gov, ChiCTR-OOh-17011878. |
| first_indexed | 2024-04-12T03:55:25Z |
| format | Article |
| id | doaj.art-d704267dc5574e2da854790e40d38dad |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T03:55:25Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-d704267dc5574e2da854790e40d38dad2022-12-22T03:48:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.940577940577Characterization of age-related immune features after autologous NK cell infusion: Protocol for an open-label and randomized controlled trialXiaofeng Tang0Biaolong Deng1Aiping Zang2Xiaowen He3Ye Zhou4Daimeng Wang5Dan Li6Xueyu Dai7Jieqiong Chen8Xuhua Zhang9Ye Liu10Yonghua Xu11Jingjing Chen12Weijie Zheng13Luding Zhang14Constance Gao15Huanfeng Yang16Bin Li17Xueqi Wang18Department of Blood Transfusion, Changzheng Hospital, Shanghai, ChinaDepartment of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Research and Development, Shanghai Origincell Medical Technology Co., Ltd., Origincell Technology Group Co., Ltd., Shanghai, ChinaDepartment of Research and Development, Shanghai Origincell Medical Technology Co., Ltd., Origincell Technology Group Co., Ltd., Shanghai, ChinaDepartment of Blood Transfusion, Changzheng Hospital, Shanghai, ChinaDepartment of Research and Development, Shanghai Origincell Medical Technology Co., Ltd., Origincell Technology Group Co., Ltd., Shanghai, ChinaDepartment of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Research and Development, Shanghai Affinity Biopharmaceutical Co., Ltd., Shanghai, ChinaDepartment of Research and Development, Shanghai Origincell Medical Technology Co., Ltd., Origincell Technology Group Co., Ltd., Shanghai, ChinaDepartment of Blood Transfusion, Changzheng Hospital, Shanghai, ChinaDepartment of Blood Transfusion, Changzheng Hospital, Shanghai, ChinaDepartment of Blood Transfusion, Changzheng Hospital, Shanghai, ChinaDepartment of Blood Transfusion, Changzheng Hospital, Shanghai, ChinaDepartment of Blood Transfusion, Changzheng Hospital, Shanghai, ChinaDepartment of Biology, College of Science, Northeastern University, Boston, MA, United StatesDepartment of Research and Development, Shanghai Origincell Medical Technology Co., Ltd., Origincell Technology Group Co., Ltd., Shanghai, ChinaDepartment of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Blood Transfusion, Changzheng Hospital, Shanghai, ChinaBackgroundAging is usually accompanied by functional declines of the immune system, especially in T-cell responses. However, little is known about ways to alleviate this.MethodsHere, 37 middle-aged healthy participants were recruited, among which 32 were intravenously administrated with expanded NK cells and 5 with normal saline. Then, we monitored changes of peripheral senescent and exhausted T cells within 4 weeks after infusion by flow cytometry, as well as serum levels of senescence-associated secretory phenotype (SASP)-related factors. In vitro co-culture assays were performed to study NK-mediated cytotoxic activity against senescent or exhausted T cells. Functional and phenotypic alteration of NK cells before and after expansion was finally characterized.ResultsAfter NK cell infusion, senescent CD28-, CD57+, CD28-CD57+, and CD28-KLRG1+ CD4+ and CD8+ T-cell populations decreased significantly, so did PD-1+ and TIM-3+ T cells. These changes were continuously observed for 4 weeks. Nevertheless, no significant changes were observed in the normal saline group. Moreover, SASP-related factors including IL-6, IL-8, IL-1α, IL-17, MIP-1α, MIP-1β, and MMP1 were significantly decreased after NK cell infusion. Further co-culture assays showed that expanded NK cells specifically and dramatically eliminated senescent CD4+ T cells other than CD28+CD4+ T cells. They also showed improved cytotoxic activity, with different expression patterns of activating and inhibitory receptors including NKG2C, NKG2A, KLRG1, LAG3, CD57, and TIM3.ConclusionOur findings imply that T-cell senescence and exhaustion is a reversible process in healthy individuals, and autologous NK cell administration can be introduced to alleviate the aging.Clinical Trial RegistrationClinicalTrials.gov, ChiCTR-OOh-17011878.https://www.frontiersin.org/articles/10.3389/fimmu.2022.940577/fullagingT-cell senescenceT-cell exhaustionnatural killer cellsSASP |
| spellingShingle | Xiaofeng Tang Biaolong Deng Aiping Zang Xiaowen He Ye Zhou Daimeng Wang Dan Li Xueyu Dai Jieqiong Chen Xuhua Zhang Ye Liu Yonghua Xu Jingjing Chen Weijie Zheng Luding Zhang Constance Gao Huanfeng Yang Bin Li Xueqi Wang Characterization of age-related immune features after autologous NK cell infusion: Protocol for an open-label and randomized controlled trial Frontiers in Immunology aging T-cell senescence T-cell exhaustion natural killer cells SASP |
| title | Characterization of age-related immune features after autologous NK cell infusion: Protocol for an open-label and randomized controlled trial |
| title_full | Characterization of age-related immune features after autologous NK cell infusion: Protocol for an open-label and randomized controlled trial |
| title_fullStr | Characterization of age-related immune features after autologous NK cell infusion: Protocol for an open-label and randomized controlled trial |
| title_full_unstemmed | Characterization of age-related immune features after autologous NK cell infusion: Protocol for an open-label and randomized controlled trial |
| title_short | Characterization of age-related immune features after autologous NK cell infusion: Protocol for an open-label and randomized controlled trial |
| title_sort | characterization of age related immune features after autologous nk cell infusion protocol for an open label and randomized controlled trial |
| topic | aging T-cell senescence T-cell exhaustion natural killer cells SASP |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.940577/full |
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