1. Autoreactive T cells targeting type II pneumocyte antigens in COVID-19 convalescent patients.
- Author
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Lichtensteiger C, Koblischke M, Berner F, Jochum AK, Sinnberg T, Balciunaite B, Purde MT, Walter V, Abdou MT, Hofmeister K, Kohler P, Vernazza P, Albrich WC, Kahlert CR, Zoufaly A, Traugott MT, Kern L, Pietsch U, Kleger GR, Filipovic M, Kneilling M, Cozzio A, Pop O, Bomze D, Bergthaler A, Hasan Ali O, Aberle J, and Flatz L
- Subjects
- Humans, Male, Female, Middle Aged, Aged, T-Lymphocytes immunology, Adult, Severity of Illness Index, Convalescence, Autoimmunity, COVID-19 immunology, SARS-CoV-2 immunology, Alveolar Epithelial Cells immunology, Alveolar Epithelial Cells metabolism, Autoantigens immunology
- Abstract
Background: The role of autoreactive T cells on the course of Coronavirus disease-19 (COVID-19) remains elusive. Type II pneumocytes represent the main target cells of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Autoimmune responses against antigens highly expressed in type II pneumocytes may influence the severity of COVID-19 disease., Objective: The aim of this study was to investigate autoreactive T cell responses against self-antigens highly expressed in type II pneumocytes in the blood of COVID-19 patients with severe and non-severe disease., Methods: We collected blood samples of COVID-19 patients with varying degrees of disease severity and of pre-pandemic controls. T cell stimulation assays with peptide pools of type II pneumocyte antigens were performed in two independent cohorts to analyze the autoimmune T cell responses in patients with non-severe and severe COVID-19 disease. Target cell lysis assays were performed with lung cancer cell lines to determine the extent of cell killing by type II PAA-specific T cells., Results: We identified autoreactive T cell responses against four recently described self-antigens highly expressed in type II pneumocytes, known as surfactant protein A, surfactant protein B, surfactant protein C and napsin A, in the blood of COVID-19 patients. These antigens were termed type II pneumocyte-associated antigens (type II PAAs). We found that patients with non-severe COVID-19 disease showed a significantly higher frequency of type II PAA-specific autoreactive T cells in the blood when compared to severely ill patients. The presence of high frequencies of type II PAA-specific T cells in the blood of non-severe COVID-19 patients was independent of their age. We also found that napsin A-specific T cells from convalescent COVID-19 patients could kill lung cancer cells, demonstrating the functional and cytotoxic role of these T cells., Conclusions: Our data suggest that autoreactive type II PAA-specific T cells have a protective role in SARS-CoV-2 infections and the presence of high frequencies of these autoreactive T cells indicates effective viral control in COVID-19 patients. Type II-PAA-specific T cells may therefore promote the killing of infected type II pneumocytes and viral clearance., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
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