Upregulation of CCR4 in activated CD8 + T cells indicates enhanced lung homing in patients with severe acute SARS‐CoV‐2 infection
| Autor: | Gloria Lutzny-Geier, Patrick Löffler, Heiko Bruns, Lucie Heinzerling, Thomas Winkler, Marcel Vetter, Simon Völkl, Andreas E. Kremer, Pauline Koch, Michael Aigner, Andreas Mackensen, Matthias Tenbusch, Nina Eisenhauer, Benjamin Frey, Silvia Spoerl, Markus F. Neurath, Gerhard Krönke, Lina Meretuk, Anita N. Kremer, Clara Maier, Klaus Überla |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine Receptors CCR4 Pulmonary toxicity Immunology Immunity to infection CCR4 Lung homing CD8-Positive T-Lymphocytes Biology Lymphocyte Activation Severity of Illness Index SARS‐CoV‐2 Pathogenesis Clinical 03 medical and health sciences Chemokine receptor 0302 clinical medicine Immune system Downregulation and upregulation COVID‐19 medicine Humans Immunology and Allergy Cytotoxic T cell Lung Research Articles Research Article|Clinical SARS-CoV-2 COVID-19 Middle Aged Up-Regulation 030104 developmental biology medicine.anatomical_structure T‐cell activation Female 030215 immunology |
| Zdroj: | European Journal of Immunology |
| ISSN: | 1521-4141 0014-2980 |
| DOI: | 10.1002/eji.202049135 |
| Popis: | COVID‐19 is a life‐threatening disease leading to bilateral pneumonia and respiratory failure. The underlying reasons why a smaller percentage of patients present with severe pulmonary symptoms whereas the majority is only mildly affected are to date not well understood. Comparing the immunological phenotype in healthy donors and patients with mild versus severe COVID‐19 shows that in COVID‐19 patients, NK‐/B‐cell activation and proliferation are enhanced independent of severity. As an important precondition for effective antibody responses, T‐follicular helper cells and antibody secreting cells are increased both in patients with mild and severe SARS‐CoV‐2 infection. Beyond this, T cells in COVID‐19 patients exhibit a stronger activation profile with differentiation toward effector cell phenotypes. Importantly, when looking at the rates of pulmonary complications in COVID‐19 patients, the chemokine receptor CCR4 is higher expressed by both CD4 and CD8 T cells of patients with severe COVID‐19. This raises the hypothesis that CCR4 upregulation on T cells in the pathogenesis of COVID‐19 promotes stronger T‐cell attraction to the lungs leading to increased immune activation with presumably higher pulmonary toxicity. Our study contributes significantly to the understanding of the immunological changes during COVID‐19, as new therapeutic agents, preferentially targeting the immune system, are highly warranted. Patients with mild COVID‐19 after SARS‐CoV2 infection exhibit increased T‐cell activation and induction of T‐cell exhaustion. During severe COVID‐19 patients show massive T‐cell activation and upregulation of homing receptors promoting hyperinflammation and increased lung trafficking. |
| Databáze: | OpenAIRE |
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