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

Grau-Expósito, Judith; Sánchez-Gaona, Nerea; Massana, Núria; Suppi, Marina; Astorga-Gamaza, Antonio; Perea, David; Rosado, Joel; Falcó, Anna et al. · Nat Commun · 2021

basic_science · Level V

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Abstract

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 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<sup>+</sup> T cells secreting IL-10. In convalescent patients, lung-T<sub>RM</sub> 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<sub>RM</sub> cells as important for future protection against SARS-CoV-2 infection.

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