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Peripheral and lung resident memory T cell responses against SARS-CoV-2.

ABSTRACT: Resident memory T cells (T_RM) positioned within the respiratory tract are probably required to limit SARS-CoV-2 spread and COVID-19. Importantly, T_RM are mostly non-recirculating, which reduces the window of opportunity to examine these cells in the blood as they move to the lung parenchyma. Here, we identify circulating virus-specific T cell responses during acute infection with functional, migratory and apoptotic patterns modulated by viral proteins and associated with clinical outcome. Disease severity is associated predominantly with IFNγ and IL-4 responses, increased responses against S peptides and apoptosis, whereas non-hospitalized patients have increased IL-12p70 levels, degranulation in response to N peptides and SARS-CoV-2-specific CCR7⁺ T cells secreting IL-10. In convalescent patients, lung-T_RM are frequently detected even 10 months after initial infection, in which contemporaneous blood does not reflect tissue-resident profiles. Our study highlights a balanced anti-inflammatory antiviral response associated with a better outcome and persisting T_RM cells as important for future protection against SARS-CoV-2 infection.

SUBMITTER: Grau-Exposito J

PROVIDER: S-EPMC8140108 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Peripheral and lung resident memory T cell responses against SARS-CoV-2.

Grau-Expósito Judith J Sánchez-Gaona Nerea N Massana Núria N Suppi Marina M Astorga-Gamaza Antonio A Perea David D Rosado Joel J Falcó Anna A Kirkegaard Cristina C Torrella Ariadna A Planas Bibiana B Navarro Jordi J Suanzes Paula P Álvarez-Sierra Daniel D Ayora Alfonso A Sansano Irene I Esperalba Juliana J Andrés Cristina C Antón Andrés A Ramón Y Cajal Santiago S Almirante Benito B Pujol-Borrell Ricardo R Falcó Vicenç V Burgos Joaquín J Buzón María J MJ Genescà Meritxell M

Nature communications 20210521 1

Resident memory T cells (T<sub>RM</sub>) positioned within the respiratory tract are probably required to limit SARS-CoV-2 spread and COVID-19. Importantly, T<sub>RM</sub> are mostly non-recirculating, which reduces the window of opportunity to examine these cells in the blood as they move to the lung parenchyma. Here, we identify circulating virus-specific T cell responses during acute infection with functional, migratory and apoptotic patterns modulated by viral proteins and associated with cl ...[more]

PMID: 34021148

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Project description:Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB), yet its moderate efficacy against pulmonary TB calls for improved vaccination strategies. Mucosal BCG vaccination generates superior protection against TB in animal models; however, the mechanisms of protection remain elusive. Tissue-resident memory T (TRM) cells have been implicated in protective immune responses against viral infections, but the role of TRM cells following mycobacterial infection is unknown. Using a mouse model of TB, we compared protection and lung cellular infiltrates of parenteral and mucosal BCG vaccination. Adoptive transfer and gene expression analyses of lung airway cells were performed to determine the protective capacities and phenotypes of different memory T cell subsets. In comparison to subcutaneous vaccination, intratracheal and intranasal BCG vaccination generated T effector memory and TRM cells in the lung, as defined by surface marker phenotype. Adoptive mucosal transfer of these airway-resident memory T cells into naive mice mediated protection against TB. Whereas airway-resident memory CD4+ T cells displayed a mixture of effector and regulatory phenotype, airway-resident memory CD8+ T cells displayed prototypical TRM features. Our data demonstrate a key role for mucosal vaccination-induced airway-resident T cells in the host defense against pulmonary TB. These results have direct implications for the design of refined vaccination strategies. BCG remains the only licensed vaccine against TB. Parenterally administered BCG has variable efficacy against pulmonary TB, and thus, improved prevention strategies and a more refined understanding of correlates of vaccine protection are required. Induction of memory T cells has been shown to be essential for protective TB vaccines. Mimicking the natural infection route by mucosal vaccination has been known to generate superior protection against TB in animal models; however, the mechanisms of protection have remained elusive. Here we performed an in-depth analysis to dissect the immunological mechanisms associated with superior mucosal protection in the mouse model of TB. We found that mucosal, and not subcutaneous, BCG vaccination generates lung-resident memory T cell populations that confer protection against pulmonary TB. We establish a comprehensive phenotypic characterization of these populations, providing a framework for future vaccine development.

Dataset Information

Peripheral and lung resident memory T cell responses against SARS-CoV-2.

Publications

Peripheral and lung resident memory T cell responses against SARS-CoV-2.

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