Elevated Foxp3+ double-negative T cells are associated with disease progression during HIV infection
Persistent immune activation, which occurs during the whole course of HIV infection, plays a pivotal role in CD4+ T cells depletion and AIDS progression. Furthermore, immune activation is a key factor that leads to impaired immune reconstitution after long-term effective antiretroviral therapy (ART)...
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.947647/full |
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| author | Leidan Zhang Leidan Zhang Leidan Zhang Leidan Zhang Leidan Zhang Yuqing Wei Yuqing Wei Yuqing Wei Di Wang Di Wang Juan Du Juan Du Juan Du Xinyue Wang Xinyue Wang Xinyue Wang Xinyue Wang Bei Li Bei Li Meiqing Jiang Meiqing Jiang Meiqing Jiang Mengyuan Zhang Mengyuan Zhang Mengyuan Zhang Na Chen Na Chen Na Chen Meiju Deng Meiju Deng Meiju Deng Meiju Deng Chuan Song Chuan Song Chuan Song Danying Chen Danying Chen Danying Chen Liang Wu Liang Wu Jiang Xiao Jiang Xiao Hongyuan Liang Hongyuan Liang Hongxin Zhao Hongxin Zhao Hongxin Zhao Yaxian Kong Yaxian Kong Yaxian Kong Yaxian Kong |
| author_facet | Leidan Zhang Leidan Zhang Leidan Zhang Leidan Zhang Leidan Zhang Yuqing Wei Yuqing Wei Yuqing Wei Di Wang Di Wang Juan Du Juan Du Juan Du Xinyue Wang Xinyue Wang Xinyue Wang Xinyue Wang Bei Li Bei Li Meiqing Jiang Meiqing Jiang Meiqing Jiang Mengyuan Zhang Mengyuan Zhang Mengyuan Zhang Na Chen Na Chen Na Chen Meiju Deng Meiju Deng Meiju Deng Meiju Deng Chuan Song Chuan Song Chuan Song Danying Chen Danying Chen Danying Chen Liang Wu Liang Wu Jiang Xiao Jiang Xiao Hongyuan Liang Hongyuan Liang Hongxin Zhao Hongxin Zhao Hongxin Zhao Yaxian Kong Yaxian Kong Yaxian Kong Yaxian Kong |
| author_sort | Leidan Zhang |
| collection | DOAJ |
| description | Persistent immune activation, which occurs during the whole course of HIV infection, plays a pivotal role in CD4+ T cells depletion and AIDS progression. Furthermore, immune activation is a key factor that leads to impaired immune reconstitution after long-term effective antiretroviral therapy (ART), and is even responsible for the increased risk of developing non-AIDS co-morbidities. Therefore, it’s imperative to identify an effective intervention targeting HIV-associated immune activation to improve disease management. Double negative T cells (DNT) were reported to provide immunosuppression during HIV infection, but the related mechanisms remained puzzled. Foxp3 endows Tregs with potent suppressive function to maintain immune homeostasis. However, whether DNT cells expressed Foxp3 and the accurate function of these cells urgently needed to be investigated. Here, we found that Foxp3+ DNT cells accumulated in untreated people living with HIV (PLWH) with CD4+ T cell count less than 200 cells/µl. Moreover, the frequency of Foxp3+ DNT cells was negatively correlated with CD4+ T cell count and CD4/CD8 ratio, and positively correlated with immune activation and systemic inflammation in PLWH. Of note, Foxp3+ DNT cells might exert suppressive regulation by increased expression of CD39, CD25, or vigorous proliferation (high levels of GITR and ki67) in ART-naive PLWH. Our study underlined the importance of Foxp3+ DNT cells in the HIV disease progression, and suggest that Foxp3+ DNT may be a potential target for clinical intervention for the control of immune activation during HIV infection. |
| first_indexed | 2024-12-10T08:34:13Z |
| format | Article |
| id | doaj.art-dfc38439a7c046e68499cbcb638b78c7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T08:34:13Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-dfc38439a7c046e68499cbcb638b78c72022-12-22T01:56:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.947647947647Elevated Foxp3+ double-negative T cells are associated with disease progression during HIV infectionLeidan Zhang0Leidan Zhang1Leidan Zhang2Leidan Zhang3Leidan Zhang4Yuqing Wei5Yuqing Wei6Yuqing Wei7Di Wang8Di Wang9Juan Du10Juan Du11Juan Du12Xinyue Wang13Xinyue Wang14Xinyue Wang15Xinyue Wang16Bei Li17Bei Li18Meiqing Jiang19Meiqing Jiang20Meiqing Jiang21Mengyuan Zhang22Mengyuan Zhang23Mengyuan Zhang24Na Chen25Na Chen26Na Chen27Meiju Deng28Meiju Deng29Meiju Deng30Meiju Deng31Chuan Song32Chuan Song33Chuan Song34Danying Chen35Danying Chen36Danying Chen37Liang Wu38Liang Wu39Jiang Xiao40Jiang Xiao41Hongyuan Liang42Hongyuan Liang43Hongxin Zhao44Hongxin Zhao45Hongxin Zhao46Yaxian Kong47Yaxian Kong48Yaxian Kong49Yaxian Kong50Peking University Ditan Teaching Hospital, Beijing, ChinaBeijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaBeijing Institute of Infectious Diseases, Beijing, ChinaNational Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaClinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaBeijing Institute of Infectious Diseases, Beijing, ChinaNational Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaNational Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaClinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaBeijing Institute of Infectious Diseases, Beijing, ChinaNational Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaPeking University Ditan Teaching Hospital, Beijing, ChinaBeijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaBeijing Institute of Infectious Diseases, Beijing, ChinaNational Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaNational Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaClinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaBeijing Institute of Infectious Diseases, Beijing, ChinaNational Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaBeijing Institute of Infectious Diseases, Beijing, ChinaNational Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaPeking University Ditan Teaching Hospital, Beijing, ChinaNational Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaClinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaBeijing Institute of Infectious Diseases, Beijing, ChinaNational Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaClinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaBeijing Institute of Infectious Diseases, Beijing, ChinaNational Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaBeijing Institute of Infectious Diseases, Beijing, ChinaNational Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaNational Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaClinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaNational Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaClinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaNational Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaClinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaPeking University Ditan Teaching Hospital, Beijing, ChinaNational Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaClinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaPeking University Ditan Teaching Hospital, Beijing, ChinaBeijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaBeijing Institute of Infectious Diseases, Beijing, ChinaNational Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaPersistent immune activation, which occurs during the whole course of HIV infection, plays a pivotal role in CD4+ T cells depletion and AIDS progression. Furthermore, immune activation is a key factor that leads to impaired immune reconstitution after long-term effective antiretroviral therapy (ART), and is even responsible for the increased risk of developing non-AIDS co-morbidities. Therefore, it’s imperative to identify an effective intervention targeting HIV-associated immune activation to improve disease management. Double negative T cells (DNT) were reported to provide immunosuppression during HIV infection, but the related mechanisms remained puzzled. Foxp3 endows Tregs with potent suppressive function to maintain immune homeostasis. However, whether DNT cells expressed Foxp3 and the accurate function of these cells urgently needed to be investigated. Here, we found that Foxp3+ DNT cells accumulated in untreated people living with HIV (PLWH) with CD4+ T cell count less than 200 cells/µl. Moreover, the frequency of Foxp3+ DNT cells was negatively correlated with CD4+ T cell count and CD4/CD8 ratio, and positively correlated with immune activation and systemic inflammation in PLWH. Of note, Foxp3+ DNT cells might exert suppressive regulation by increased expression of CD39, CD25, or vigorous proliferation (high levels of GITR and ki67) in ART-naive PLWH. Our study underlined the importance of Foxp3+ DNT cells in the HIV disease progression, and suggest that Foxp3+ DNT may be a potential target for clinical intervention for the control of immune activation during HIV infection.https://www.frontiersin.org/articles/10.3389/fimmu.2022.947647/fullHIVFoxp3double-negative T cellimmune activationimmune regulation |
| spellingShingle | Leidan Zhang Leidan Zhang Leidan Zhang Leidan Zhang Leidan Zhang Yuqing Wei Yuqing Wei Yuqing Wei Di Wang Di Wang Juan Du Juan Du Juan Du Xinyue Wang Xinyue Wang Xinyue Wang Xinyue Wang Bei Li Bei Li Meiqing Jiang Meiqing Jiang Meiqing Jiang Mengyuan Zhang Mengyuan Zhang Mengyuan Zhang Na Chen Na Chen Na Chen Meiju Deng Meiju Deng Meiju Deng Meiju Deng Chuan Song Chuan Song Chuan Song Danying Chen Danying Chen Danying Chen Liang Wu Liang Wu Jiang Xiao Jiang Xiao Hongyuan Liang Hongyuan Liang Hongxin Zhao Hongxin Zhao Hongxin Zhao Yaxian Kong Yaxian Kong Yaxian Kong Yaxian Kong Elevated Foxp3+ double-negative T cells are associated with disease progression during HIV infection Frontiers in Immunology HIV Foxp3 double-negative T cell immune activation immune regulation |
| title | Elevated Foxp3+ double-negative T cells are associated with disease progression during HIV infection |
| title_full | Elevated Foxp3+ double-negative T cells are associated with disease progression during HIV infection |
| title_fullStr | Elevated Foxp3+ double-negative T cells are associated with disease progression during HIV infection |
| title_full_unstemmed | Elevated Foxp3+ double-negative T cells are associated with disease progression during HIV infection |
| title_short | Elevated Foxp3+ double-negative T cells are associated with disease progression during HIV infection |
| title_sort | elevated foxp3 double negative t cells are associated with disease progression during hiv infection |
| topic | HIV Foxp3 double-negative T cell immune activation immune regulation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.947647/full |
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