Journal Article

Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia

Sita, Marco, Facchinetti, Fabio, Lo Tartaro, Domenico, Guaraldi, Giovanni, Menozzi, Marianna, Tonelli, Roberto, Franceschi, Giacomo, Fidanza, Lucia, Iannone, Anna, Cossarizza, Andrea, Borella, Rebecca, Pietrangelo, Antonello, Fantini, Riccardo, Mattioli, Marco, Brugioni, Lucio, Milić, Jovana, Girardis, Massimo, Paolini, Annamaria, Trenti, Tommaso, De Biasi, Sara, Gibellini, Lara, Cicchetti, Luca, Gozzi, Licia, Sarti, Mario, Clini, Enrico, Meschiari, Marianna, Bellinazzi, Caterina, Mussini, Cristina

2020

Overview

The immune system of patients infected by SARS-CoV-2 is severely impaired. Detailed investigation of T cells and cytokine production in patients affected by COVID-19 pneumonia are urgently required. Here we show that, compared with healthy controls, COVID-19 patients’ T cell compartment displays several alterations involving naïve, central memory, effector memory and terminally differentiated cells, as well as regulatory T cells and PD1 + CD57 + exhausted T cells. Significant alterations exist also in several lineage-specifying transcription factors and chemokine receptors. Terminally differentiated T cells from patients proliferate less than those from healthy controls, whereas their mitochondria functionality is similar in CD4 + T cells from both groups. Patients display significant increases of proinflammatory or anti-inflammatory cytokines, including T helper type-1 and type-2 cytokines, chemokines and galectins; their lymphocytes produce more tumor necrosis factor (TNF), interferon-γ, interleukin (IL)-2 and IL-17, with the last observation implying that blocking IL-17 could provide a novel therapeutic strategy for COVID-19. COVID-19 is a serious pandemic threat to public health, but insights on the pathophysiological and immunological conditions are only emerging. Here the authors use multi-color flow cytometry to characterize CD4 + and CD8 + T cells in peripheral blood from 39 COVID-19 patients in Italy to report altered T cell activation, function and polarization.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 13/21 / 13/31 / 631/250/1619/554/1898 / 631/250/2152/1566/1571 / 631/250/255/2514 / 692/420/2780/2152/1566/2493 / Adult / Aged / Aged, 80 and over / Betacoronavirus - immunology / Biomarkers - metabolism / CD4 antigen / CD4-Positive T-Lymphocytes - immunology / CD4-Positive T-Lymphocytes - metabolism / CD4-Positive T-Lymphocytes - pathology / CD57 antigen / CD8 antigen / CD8-Positive T-Lymphocytes - immunology / CD8-Positive T-Lymphocytes - metabolism / CD8-Positive T-Lymphocytes - pathology / Cell activation / Cell differentiation / Cellular Senescence / Chemokine receptors / Coronavirus Infections - blood / Coronavirus Infections - immunology / Coronavirus Infections - pathology / Coronaviruses / COVID-19 / Cytokine Release Syndrome / Cytokines / Cytokines - immunology / Cytokines - metabolism / Exhaustion / Female / Flow cytometry / Health care / Helper cells / Humanities and Social Sciences / Humans / Immune system / Immunologic Memory / Immunology / Immunoregulation / Inflammation / Interferon / Interleukin 17 / Italy - epidemiology / Lymphocyte Activation / Lymphocyte Count / Lymphocytes / Lymphocytes T / Male / Memory cells / Middle Aged / Mitochondria / multidisciplinary / Pandemics / PD-1 protein / Peripheral blood / Pneumonia / Pneumonia, Viral - blood / Pneumonia, Viral - immunology / Pneumonia, Viral - pathology / Public health / SARS-CoV-2 / Science / Science (multidisciplinary) / Senescence / Severe acute respiratory syndrome coronavirus 2 / T-Lymphocyte Subsets - immunology / T-Lymphocyte Subsets - metabolism / T-Lymphocyte Subsets - pathology / Th17 Cells - immunology / Th17 Cells - metabolism / Th17 Cells - pathology / Transcription factors / Tumor necrosis factor / Tumor necrosis factor-TNF / γ-Interferon