tetano
Editor, Senior Moderator
J Autoimmun
. 2023 Oct 10:140:103118.
doi: 10.1016/j.jaut.2023.103118. Online ahead of print. Autoreactive T cells targeting type II pneumocyte antigens in COVID-19 convalescent patients
Christa Lichtensteiger[SUP] 1 [/SUP], Maximilian Koblischke[SUP] 2 [/SUP], Fiamma Berner[SUP] 1 [/SUP], Ann-Kristin Jochum[SUP] 3 [/SUP], Tobias Sinnberg[SUP] 4 [/SUP], Beatrice Balciunaite[SUP] 5 [/SUP], Mette-Triin Purde[SUP] 1 [/SUP], Vincent Walter[SUP] 5 [/SUP], Marie-Therese Abdou[SUP] 1 [/SUP], Kathrin Hofmeister[SUP] 5 [/SUP], Philipp Kohler[SUP] 6 [/SUP], Pietro Vernazza[SUP] 6 [/SUP], Werner C Albrich[SUP] 6 [/SUP], Christian R Kahlert[SUP] 6 [/SUP], Alexander Zoufaly[SUP] 7 [/SUP], Marianna T Traugott[SUP] 8 [/SUP], Lukas Kern[SUP] 9 [/SUP], Urs Pietsch[SUP] 10 [/SUP], Gian-Reto Kleger[SUP] 11 [/SUP], Miodrag Filipovic[SUP] 10 [/SUP], Manfred Kneilling[SUP] 12 [/SUP], Antonio Cozzio[SUP] 13 [/SUP], Oltin Pop[SUP] 1 [/SUP], David Bomze[SUP] 14 [/SUP], Andreas Bergthaler[SUP] 15 [/SUP], Omar Hasan Ali[SUP] 16 [/SUP], Judith Aberle[SUP] 2 [/SUP], Lukas Flatz[SUP] 17 [/SUP]
Affiliations
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.
Keywords: Autoantigen; Autoimmunity; COVID-19; SARS-CoV-2; type II pneumocyte.
. 2023 Oct 10:140:103118.
doi: 10.1016/j.jaut.2023.103118. Online ahead of print. Autoreactive T cells targeting type II pneumocyte antigens in COVID-19 convalescent patients
Christa Lichtensteiger[SUP] 1 [/SUP], Maximilian Koblischke[SUP] 2 [/SUP], Fiamma Berner[SUP] 1 [/SUP], Ann-Kristin Jochum[SUP] 3 [/SUP], Tobias Sinnberg[SUP] 4 [/SUP], Beatrice Balciunaite[SUP] 5 [/SUP], Mette-Triin Purde[SUP] 1 [/SUP], Vincent Walter[SUP] 5 [/SUP], Marie-Therese Abdou[SUP] 1 [/SUP], Kathrin Hofmeister[SUP] 5 [/SUP], Philipp Kohler[SUP] 6 [/SUP], Pietro Vernazza[SUP] 6 [/SUP], Werner C Albrich[SUP] 6 [/SUP], Christian R Kahlert[SUP] 6 [/SUP], Alexander Zoufaly[SUP] 7 [/SUP], Marianna T Traugott[SUP] 8 [/SUP], Lukas Kern[SUP] 9 [/SUP], Urs Pietsch[SUP] 10 [/SUP], Gian-Reto Kleger[SUP] 11 [/SUP], Miodrag Filipovic[SUP] 10 [/SUP], Manfred Kneilling[SUP] 12 [/SUP], Antonio Cozzio[SUP] 13 [/SUP], Oltin Pop[SUP] 1 [/SUP], David Bomze[SUP] 14 [/SUP], Andreas Bergthaler[SUP] 15 [/SUP], Omar Hasan Ali[SUP] 16 [/SUP], Judith Aberle[SUP] 2 [/SUP], Lukas Flatz[SUP] 17 [/SUP]
Affiliations
- PMID: 37826919
- DOI: 10.1016/j.jaut.2023.103118
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.
Keywords: Autoantigen; Autoimmunity; COVID-19; SARS-CoV-2; type II pneumocyte.