Autoreactive T cells targeting type II pneumocyte antigens in COVID-19 convalescent patients.

Autoantigen Autoimmunity COVID-19 SARS-CoV-2 type II pneumocyte

Journal

Journal of autoimmunity
ISSN: 1095-9157
Titre abrégé: J Autoimmun
Pays: England
ID NLM: 8812164

Informations de publication

Date de publication:
10 Oct 2023
Historique:
received: 09 03 2023
revised: 21 09 2023
accepted: 25 09 2023
medline: 13 10 2023
pubmed: 13 10 2023
entrez: 12 10 2023
Statut: aheadofprint

Résumé

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. 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. 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. 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. 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.

Sections du résumé

BACKGROUND 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 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 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 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 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.

Identifiants

DOI: 10.1016/j.jaut.2023.103118 PMID: 37826919
pubmed: 37826919
pii: S0896-8411(23)00127-0
doi: 10.1016/j.jaut.2023.103118
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

103118

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Auteurs

Christa Lichtensteiger (C)

Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Maximilian Koblischke (M)

Center for Virology, Medical University of Vienna, Vienna, Austria.

Fiamma Berner (F)

Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Ann-Kristin Jochum (AK)

Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Insitute of Pathology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Tobias Sinnberg (T)

Department of Dermatology, Eberhard Karls University Hospital Tübingen, Tübingen, Germany; Cluster of Excellence iFIT (EXC 2180) Image-Guided and Functionally Instructed Tumor Therapies, Eberhard Karls University Hospital Tübingen, Tübingen, Germany.

Beatrice Balciunaite (B)

Department of Dermatology, Eberhard Karls University Hospital Tübingen, Tübingen, Germany.

Mette-Triin Purde (MT)

Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Vincent Walter (V)

Department of Dermatology, Eberhard Karls University Hospital Tübingen, Tübingen, Germany.

Marie-Therese Abdou (MT)

Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Kathrin Hofmeister (K)

Department of Dermatology, Eberhard Karls University Hospital Tübingen, Tübingen, Germany.

Philipp Kohler (P)

Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Pietro Vernazza (P)

Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Werner C Albrich (WC)

Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Christian R Kahlert (CR)

Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Alexander Zoufaly (A)

Department of Medicine IV, Clinic Favoriten, Vienna Healthcare Group, Vienna, Austria; Faculty of Medicine, Sigmund Freud University Vienna, Austria.

Marianna T Traugott (MT)

Department of Medicine IV, Clinic Favoriten, Vienna Healthcare Group, Vienna, Austria.

Lukas Kern (L)

Department of Pneumology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Urs Pietsch (U)

Surgical Intensive Care Unit, Division of Anaesthesiology, Intensive Care, Rescue and Pain Medicine, Kantonsspital St. Gallen, Switzerland.

Gian-Reto Kleger (GR)

Division of Intensive Care Medicine, Kantonsspital St. Gallen, Switzerland.

Miodrag Filipovic (M)

Surgical Intensive Care Unit, Division of Anaesthesiology, Intensive Care, Rescue and Pain Medicine, Kantonsspital St. Gallen, Switzerland.

Manfred Kneilling (M)

Department of Dermatology, Eberhard Karls University Hospital Tübingen, Tübingen, Germany; Cluster of Excellence iFIT (EXC 2180) Image-Guided and Functionally Instructed Tumor Therapies, Eberhard Karls University Hospital Tübingen, Tübingen, Germany; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University of Tübingen, Germany.

Antonio Cozzio (A)

Department of Dermatology, Venereology and Allergology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Oltin Pop (O)

Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

David Bomze (D)

Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Sackler Faculty of Medicine, Tel Aviv University; Tel Aviv, Israel.

Andreas Bergthaler (A)

Institute for Hygiene and Applied Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria; CeMM Research Center for Molecular Medicine or the Austrian Academy of Sciences, Vienna, Austria.

Omar Hasan Ali (O)

Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Dermatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, Canada.

Judith Aberle (J)

Center for Virology, Medical University of Vienna, Vienna, Austria.

Lukas Flatz (L)

Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Dermatology, Eberhard Karls University Hospital Tübingen, Tübingen, Germany; Department of Dermatology, Venereology and Allergology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Dermatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Department of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland. Electronic address: lukas.flatz@med.uni-tuebingen.de.

Classifications MeSH