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J Leukoc Biol ; 109(1): 91-97, 2021 01.
Article in English | MEDLINE | ID: covidwho-1188013


Regulatory T cell can protect against severe forms of coronaviral infections attributable to host inflammatory responses. But its role in the pathogenesis of COVID-19 is still unclear. In this study, frequencies of total and multiple subsets of lymphocytes in peripheral blood of COVID-19 patients and discharged individuals were analyzed using a multicolor flow cytometry assay. Plasma concentration of IL-10 was measured using a microsphere-based immunoassay kit. Comparing to healthy controls, the frequencies of total lymphocytes and T cells decreased significantly in both acutely infected COVID-19 patients and discharged individuals. The frequencies of total lymphocytes correlated negatively with the frequencies of CD3- CD56+ NK cells. The frequencies of regulatory CD8+ CD25+ T cells correlated with CD4+ /CD8+ T cell ratios positively, while the frequencies of regulatory CD4+ CD25+ CD127- T cells correlated negatively with CD4+ /CD8+ T cell ratios. Ratios of CD4+ /CD8+ T cells increased significantly in patients beyond age of 45 years. And accordingly, the frequencies of regulatory CD8+ CD25+ T cells were also found significantly increased in these patients. Collectively, the results suggest that regulatory CD4+ and CD8+ T cells may play distinct roles in the pathogenesis of COVID-19. Moreover, the data indicate that NK cells might contribute to the COVID-19 associated lymphopenia.

CD8-Positive T-Lymphocytes , COVID-19 , SARS-CoV-2 , T-Lymphocytes, Regulatory , Adult , Aged , Antigens, CD/blood , Antigens, CD/immunology , CD4-CD8 Ratio , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/pathology , COVID-19/blood , COVID-19/immunology , COVID-19/pathology , Female , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , T-Lymphocytes, Regulatory/pathology
JCI Insight ; 6(6)2021 03 22.
Article in English | MEDLINE | ID: covidwho-1088356


Regulatory T (Treg) cells orchestrate resolution and repair of acute lung inflammation and injury after viral pneumonia. Compared with younger patients, older individuals experience impaired recovery and worse clinical outcomes after severe viral infections, including influenza and SARS coronavirus 2 (SARS-CoV-2). Whether age is a key determinant of Treg cell prorepair function after lung injury remains unknown. Here, we showed that aging results in a cell-autonomous impairment of reparative Treg cell function after experimental influenza pneumonia. Transcriptional and DNA methylation profiling of sorted Treg cells provided insight into the mechanisms underlying their age-related dysfunction, with Treg cells from aged mice demonstrating both loss of reparative programs and gain of maladaptive programs. Strategies to restore youthful Treg cell functional programs could be leveraged as therapies to improve outcomes among older individuals with severe viral pneumonia.

Aging/physiology , Influenza A virus , Influenza, Human/pathology , Lung/pathology , Pneumonia, Viral/pathology , SARS-CoV-2 , T-Lymphocytes, Regulatory/pathology , Age Factors , Aging/metabolism , Animals , COVID-19/complications , COVID-19/metabolism , COVID-19/pathology , COVID-19/virology , Humans , Influenza, Human/complications , Influenza, Human/metabolism , Influenza, Human/virology , Lung/metabolism , Mice, Inbred C57BL , Pneumonia, Viral/etiology , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , T-Lymphocytes, Regulatory/metabolism
Immunology ; 160(3): 261-268, 2020 07.
Article in English | MEDLINE | ID: covidwho-381740


Coronavirus disease 2019 (COVID-19) is a respiratory disorder caused by the highly contagious severe acute respiratory syndrome coronavirus 2. The immunopathological characteristics of patients with COVID-19, either systemic or local, have not been thoroughly studied. In the present study, we analysed both the changes in the number of various immune cell types as well as cytokines important for immune reactions and inflammation. Our data indicate that patients with severe COVID-19 exhibited an overall decline of lymphocytes including CD4+ and CD8+ T cells, B cells and natural killer cells. The number of immunosuppressive regulatory T cells was moderately increased in patients with mild COVID-19. Interleukin-6 (IL-6), IL-10 and C-reactive protein were remarkably up-regulated in patients with severe COVID-19. In conclusion, our study shows that the comprehensive decrease of lymphocytes, and the elevation of IL-6, IL-10 and C-reactive protein are reliable indicators of severe COVID-19.

Coronavirus Infections/immunology , Coronavirus Infections/pathology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Aged , B-Lymphocytes/immunology , B-Lymphocytes/pathology , Betacoronavirus/physiology , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Female , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Lymphocytes/pathology , Male , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , SARS-CoV-2 , Severity of Illness Index , T-Lymphocytes/immunology , T-Lymphocytes/pathology , T-Lymphocytes, Regulatory/pathology