Persistent T cell proliferation and MDSCs expansion precede incomplete CD4+ T cell recovery in people with acute HIV-1 infection with early ART
HIV-1 infection causes T cell dysfunction that cannot be fully restored by anti-retroviral therapy (ART). Myeloid-derived suppressor cells (MDSCs) expand and suppress T cell function during viral infection. In this study, we evaluated the dynamics of phenotypes and function of T cells and MDSCs and...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023027974 |
| _version_ | 1797815666640683008 |
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| author | Zhen Li Ping Yan Rui Wang Xiaofan Lu Yang Zhang Bin Su Xin Zhang Lin Yuan Zhiying Liu Wei Jiang Tong Zhang Hao Wu Xiaojie Huang |
| author_facet | Zhen Li Ping Yan Rui Wang Xiaofan Lu Yang Zhang Bin Su Xin Zhang Lin Yuan Zhiying Liu Wei Jiang Tong Zhang Hao Wu Xiaojie Huang |
| author_sort | Zhen Li |
| collection | DOAJ |
| description | HIV-1 infection causes T cell dysfunction that cannot be fully restored by anti-retroviral therapy (ART). Myeloid-derived suppressor cells (MDSCs) expand and suppress T cell function during viral infection. In this study, we evaluated the dynamics of phenotypes and function of T cells and MDSCs and the effects of their interaction on CD4+ T cell reconstitution in people with acute HIV-1 infection (PWAH) with early ART. Flow cytometry was used to detect the phenotypic dynamics and function of T cells and MDSCs at pre-ART, 4, 24, 48, and 96 weeks of ART. We observed that T cells were hyper-activated and hyper-proliferative in PWAH at pre-ART. Early ART normalized T cell activation but not their proliferation. T cell proliferation, enriched in PD-1+ T cells, was persisted and negatively associated with CD4+ T-cell counts after ART. Moreover, M-MDSCs frequency was increased and positively correlated with T cell proliferation after 96 weeks of ART. M-MDSCs persisted and inhibited T cell proliferation ex vivo, which could be partially reversed by PD-L1 blockade. Further, we found higher frequencies of proliferative CD4+ T cells and M-MDSCs in PWAH with lower CD4+ T cell numbers (<500 cells/μL) compared to PWAH with higher CD4+ T cell numbers (>600 cells/μL) after 96 weeks of ART. Our findings indicate that persistent T cell proliferation, MDSCs expansion, and their interaction may affect CD4+ T-cell recovery in PWAH with early ART. |
| first_indexed | 2024-03-13T08:26:11Z |
| format | Article |
| id | doaj.art-c8e7f8d4d9a348ef856f4eed6cad4d37 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-13T08:26:11Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-c8e7f8d4d9a348ef856f4eed6cad4d372023-05-31T04:44:51ZengElsevierHeliyon2405-84402023-05-0195e15590Persistent T cell proliferation and MDSCs expansion precede incomplete CD4+ T cell recovery in people with acute HIV-1 infection with early ARTZhen Li0Ping Yan1Rui Wang2Xiaofan Lu3Yang Zhang4Bin Su5Xin Zhang6Lin Yuan7Zhiying Liu8Wei Jiang9Tong Zhang10Hao Wu11Xiaojie Huang12Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China; Corresponding author.Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaDepartment of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA; Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC, USABeijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China; Corresponding author.Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China; Corresponding author.HIV-1 infection causes T cell dysfunction that cannot be fully restored by anti-retroviral therapy (ART). Myeloid-derived suppressor cells (MDSCs) expand and suppress T cell function during viral infection. In this study, we evaluated the dynamics of phenotypes and function of T cells and MDSCs and the effects of their interaction on CD4+ T cell reconstitution in people with acute HIV-1 infection (PWAH) with early ART. Flow cytometry was used to detect the phenotypic dynamics and function of T cells and MDSCs at pre-ART, 4, 24, 48, and 96 weeks of ART. We observed that T cells were hyper-activated and hyper-proliferative in PWAH at pre-ART. Early ART normalized T cell activation but not their proliferation. T cell proliferation, enriched in PD-1+ T cells, was persisted and negatively associated with CD4+ T-cell counts after ART. Moreover, M-MDSCs frequency was increased and positively correlated with T cell proliferation after 96 weeks of ART. M-MDSCs persisted and inhibited T cell proliferation ex vivo, which could be partially reversed by PD-L1 blockade. Further, we found higher frequencies of proliferative CD4+ T cells and M-MDSCs in PWAH with lower CD4+ T cell numbers (<500 cells/μL) compared to PWAH with higher CD4+ T cell numbers (>600 cells/μL) after 96 weeks of ART. Our findings indicate that persistent T cell proliferation, MDSCs expansion, and their interaction may affect CD4+ T-cell recovery in PWAH with early ART.http://www.sciencedirect.com/science/article/pii/S2405844023027974Acute HIV-1 infectionT cell proliferationMDSCsEarly ARTImmune reconstitutionImmune activation |
| spellingShingle | Zhen Li Ping Yan Rui Wang Xiaofan Lu Yang Zhang Bin Su Xin Zhang Lin Yuan Zhiying Liu Wei Jiang Tong Zhang Hao Wu Xiaojie Huang Persistent T cell proliferation and MDSCs expansion precede incomplete CD4+ T cell recovery in people with acute HIV-1 infection with early ART Heliyon Acute HIV-1 infection T cell proliferation MDSCs Early ART Immune reconstitution Immune activation |
| title | Persistent T cell proliferation and MDSCs expansion precede incomplete CD4+ T cell recovery in people with acute HIV-1 infection with early ART |
| title_full | Persistent T cell proliferation and MDSCs expansion precede incomplete CD4+ T cell recovery in people with acute HIV-1 infection with early ART |
| title_fullStr | Persistent T cell proliferation and MDSCs expansion precede incomplete CD4+ T cell recovery in people with acute HIV-1 infection with early ART |
| title_full_unstemmed | Persistent T cell proliferation and MDSCs expansion precede incomplete CD4+ T cell recovery in people with acute HIV-1 infection with early ART |
| title_short | Persistent T cell proliferation and MDSCs expansion precede incomplete CD4+ T cell recovery in people with acute HIV-1 infection with early ART |
| title_sort | persistent t cell proliferation and mdscs expansion precede incomplete cd4 t cell recovery in people with acute hiv 1 infection with early art |
| topic | Acute HIV-1 infection T cell proliferation MDSCs Early ART Immune reconstitution Immune activation |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023027974 |
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