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

Abstract

Resident memory T cells (TRM) positioned within the respiratory tract are probably required to limit SARS-CoV-2 spread and COVID-19. Importantly, TRM 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-TRM 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 TRM cells as important for future protection against SARS-CoV-2 infection.

Tissue resident memory T cells in the respiratory tract

“…More recently it has been demonstrated that lung CD4 + and CD8 + Trm were present in SARS-CoV-2-infected patients and reduced disease severity was shown to be associated with increased numbers of airway CD4 + and CD8 + Trm 104 , 105 . These Trm cells produced IFNγ upon in vitro stimulation and importantly persisted for at least 10 months in convalescent patients 104 , 106 . Although less is known about SARS-CoV-2-specific Trm, it has been reported that the depletion of CD8 + T cells in non-human primates prior to re-challenge with SARS-CoV-2 resulted in elevated viral titers in the nasal tissue, which may indicate a role for nasal CD8 + Trm in protection 107 .…”

T cell immunity to SARS-CoV-2

“…SARS-CoV-2 infection induces a virus-specific T cell immunity that can be detected at least 8 months after infection in peripheral blood, but analyses on tissue samples are scarce. Recently, preliminary studies on lung and nasal tissue obtained from SARS-CoV-2 convalescent individuals have found T RM responses with functional reactivity against several SARS-CoV-2 proteins that persist for at least 2 to 10 months after infection [ 112 , 113 ]. Virus-specific T RMs located in the upper respiratory tract are known to be long-lived [ 114 ], but further studies are required to determine the longevity of SARS-CoV-2-specific T RMs in the lower respiratory tract, given that studies in mice have demonstrate their gradual loss in the lung [ 115 ].…”

SARS-CoV-2 Portrayed against HIV: Contrary Viral Strategies in Similar Disguise

“…Indeed, delayed or insufficient activation of T cell responses may lead to severe lung damage or systemic inflammation, whereas early induction of functional SARS-CoV-2-specific T cells is associated with rapid viral clearance and mild disease in COVID-19 patients [ 448 , 449 , 450 ]. In agreement with analyses in the blood, functional and consistent CD8 + resident-memory (TRM) and CD4 + T-helper-17 (TH17) cells in bronchoalveolar lavages were associated with beneficial outcomes [ 451 , 452 ]. Both CD4 + and CD8 + T cell responses to SARS-CoV-2 have been determined as important parameters associated with control of SARS-CoV-2 infection, yet CD4 + T cell responses appear even more prominent than CD8 + T cell responses [ 221 , 443 , 444 , 453 ].…”