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PD-1 blockade counteracts post-COVID-19 immune abnormalities and stimulates the anti-SARS-CoV-2 immune response

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单位: [1]Univ Milan, Int Ctr T1D, Pediat Clin Res Ctr Romeo & Enrica Invernizzi, Dept Biomed & Clin Sci L Sacco, Milan, Italy [2]Harvard Med Sch, Boston Childrens Hosp, Nephrol Div, 300 Longwood Ave Enders Bldg, Boston, MA 02115 USA [3]ASST Fatebenefratelli Sacco, Div Resp Dis, Milan, Italy [4]Univ Milan, Dept Biomed & Clin Sci L Sacco, Milan, Italy [5]Huazhong Univ Sci & Technol,Tongji Hosp & Med Coll,Inst Organ Transplantat,Wuhan,Peoples R China [6]Al Azhar Univ, Med, Cairo, Egypt [7]Brigham & Womens Hosp, Transplantat Res Ctr, Nephrol Div, 75 Francis St, Boston, MA 02115 USA [8]ASST Fatebenefratelli Sacco, Endocrinol Div, Milan, Italy [9]ASST Fatebenefratelli Sacco, Div Trop Dis, Milan, Italy [10]ASST Fatebenefratelli Sacco, Div Infect Dis, Milan, Italy [11]Univ Milan, Pediat Clin Res Ctr Romeo & Enrica Invernizzi, Dept Biomed & Clin Sci L Sacco, Milan, Italy [12]Buzzi Childrens Hosp, Dept Pediat, Milan, Italy [13]ASST Ovest Milanese, Infect Dis Unit, Legnano Gen Hosp, Legnano, Italy
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A substantial proportion of patients who have recovered from coronavirus disease-2019 (COVID-19) experience COVID-19-related symptoms even months after hospital discharge. We extensively immunologically characterized patients who recovered from COVID-19. In these patients, T cells were exhausted, with increased PD-1(+) T cells, as compared with healthy controls. Plasma levels of IL-1 beta, IL-1RA, and IL-8, among others, were also increased in patients who recovered from COVID-19. This altered immunophenotype was mirrored by a reduced ex vivo T cell response to both nonspecific and specific stimulation, revealing a dysfunctional status of T cells, including a poor response to SARS-CoV-2 antigens. Altered levels of plasma soluble PD-L1, as well as of PD1 promoter methylation and PD1-targeting miR-15-5p, in CD8(+) T cells were also observed, suggesting abnormal function of the PD-1/PD-L1 immune checkpoint axis. Notably, ex vivo blockade of PD-1 nearly normalized the aforementioned immunophenotype and restored T cell function, reverting the observed post-COVID-19 immune abnormalities; indeed, we also noted an increased T cellmediated response to SARS-CoV-2 peptides. Finally, in a neutralization assay, PD-1 blockade did not alter the ability of T cells to neutralize SARS-CoV-2 spike pseudotyped lentivirus infection. Immune checkpoint blockade ameliorates post-COVID-19 immune abnormalities and stimulates an anti-SARS-CoV-2 immune response.

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出版当年[2020]版:
大类 | 2 区 医学
小类 | 2 区 医学:研究与实验
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 医学:研究与实验
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出版当年[2019]版:
Q1 MEDICINE, RESEARCH & EXPERIMENTAL
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Q1 MEDICINE, RESEARCH & EXPERIMENTAL

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第一作者单位: [1]Univ Milan, Int Ctr T1D, Pediat Clin Res Ctr Romeo & Enrica Invernizzi, Dept Biomed & Clin Sci L Sacco, Milan, Italy
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通讯机构: [1]Univ Milan, Int Ctr T1D, Pediat Clin Res Ctr Romeo & Enrica Invernizzi, Dept Biomed & Clin Sci L Sacco, Milan, Italy [2]Harvard Med Sch, Boston Childrens Hosp, Nephrol Div, 300 Longwood Ave Enders Bldg, Boston, MA 02115 USA [8]ASST Fatebenefratelli Sacco, Endocrinol Div, Milan, Italy
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