Temporal changes in T cell subsets and expansion of cytotoxic CD4+ T cells in the lungs in severe COVID-19
Many studies have been performed in severe COVID-19 on immune cells in the circulation and on cells obtained by bronchoalveolar lavage. Most studies have tended to provide relative information rather than a quantitative view, and it is a combination of approaches by various groups that is helping th...
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Veröffentlicht in: | Clinical immunology (Orlando, Fla.) Fla.), 2022-04, Vol.237, p.108991-108991, Article 108991 |
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Zusammenfassung: | Many studies have been performed in severe COVID-19 on immune cells in the circulation and on cells obtained by bronchoalveolar lavage. Most studies have tended to provide relative information rather than a quantitative view, and it is a combination of approaches by various groups that is helping the field build a picture of the mechanisms that drive severe lung disease. Approaches employed to date have not revealed information on lung parenchymal T cell subsets in severe COVID-19. Therefore, we sought to examine early and late T cell subset alterations in the lungs and draining lymph nodes in severe COVID-19 using a rapid autopsy protocol and quantitative imaging approaches. Here, we have established that cytotoxic CD4+ T cells (CD4 + CTLs) increase in the lungs, draining lymph nodes and blood as COVID-19 progresses. CD4 + CTLs are prominently expanded in the lung parenchyma in severe COVID-19. In contrast CD8+ T cells are not prominent, exhibit increased PD-1 expression, and no obvious increase is seen in the number of Granzyme B+ CD8+ T cells in the lung parenchyma in severe COVID-19. Based on quantitative evidence for re-activation in the lung milieu, CD4 + CTLs may be as likely to drive viral clearance as CD8+ T cells and may also be contributors to lung inflammation and eventually to fibrosis in severe COVID-19.
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•CD4 + CTLs were the only T cell subset that were significantly expanded in the lungs in severe COVID-19.•The majority of CD8+ T cells in the lungs in severe COVID-19 express PD-1.•Re-activated GZMB+ CD8 + CTLs and GZMB+ CD4 + CTLs were found in equivalent proportions in the lungs.•CD4 + CTLs were prominent in the circulation, were SARS-CoV-2 specific and this expansion was linked to disease severity. |
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ISSN: | 1521-6616 1521-7035 1521-7035 |
DOI: | 10.1016/j.clim.2022.108991 |