SARS-CoV-2 infection generates tissue-localized immunological memory in humans

Abstract

Adaptive immune responses to SARS-CoV-2 infection have been extensively characterized in blood; however, most functions of protective immunity must be accomplished in tissues. Here, we report from examination of SARS-CoV-2 seropositive organ donors (ages 10 -74) that CD4 + T, CD8 + T, and B cell memory generated in response to infection is present in bone marrow, spleen, lung, and multiple lymph nodes (LNs) for up to 6 months post-infection. Lungs and lung-associated LNs were the most prevalent sites for SARS-CoV-2-specific memory T and B cells, with significant correlations between circulating and tissue-resident memory T and B cells in all sites. We further identified SARS-CoV-2-specific germinal centers in the lung-associated LNs up to 6 months post-infection. SARS-CoV-2-specific follicular helper T cells were also abundant in lung-associated LNs and lungs. Together, the results indicate local tissue coordination of cellular and humoral immune memory against SARS-CoV-2 for site-specific protection against future infectious challenges.

The germinal centre B cell response to SARS-CoV-2

“…The presence of long-lived plasma cells in the bone marrow of SARS-CoV-2-infected individuals further supports this model, as high-affinity plasma cells are predominantly derived from GCs 42 , 64 . Indeed, a robust GC and T FH cell response that persists for up to 6 months has been identified in humans and rhesus macaques following SARS-CoV-2 infection 65 , 66 .…”

“…B cells are found in many mucosal tissues in humans 154 . SARS-CoV-2 infection induces virus-specific memory B cells in the bone marrow, spleen, lungs and lymph nodes 66 . Residual antigen depots are also present in mucosal tissues, including in the gut, following SARS-CoV-2 infection, and may fuel the continued clonal evolution of B cells in these sites 40 , 63 , 155 .…”

Heterogeneity of human anti-viral immunity shaped by virus, tissue, age, and sex

“…However, blood contains a small fraction of the total immune cells throughout the body and lacks tissue-resident immune cells , including TRM (Farber, 2021;Poon and Farber, 2020;Weisberg et al, 2021b). The generation of memory T cell responses to infection and vaccination can be followed in peripheral blood (Akondy et al, 2017;Dan et al, 2021;Graham et al, 2020;Hammarlund et al, 2003;Thom et al, 2021), though studies of infection or vaccination sites have revealed distinct dynamics, functions, and immune cell compositions compared with blood (Guvenel et al, 2020;Patel et al, 2018;Szabo et al, 2021;Poon et al, 2021). Defining the full heterogeneity of virus-specific T cell responses therefore requires comprehensive profiling across multiple sites.…”

A live attenuated influenza virus-vectored intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2 infection

“…In this study, we also observed the activation and secretion of antiviral cytokines and chemokines in lung tissue from vaccinated mice and correlated their production with rapid protection in hamsters. (ii) We believe that robust and local RBD-specific T cell responses should contribute to providing effective protection against SARS-CoV-2 infection 37 . Considering resident memory CD8 + T cells, which are thought to provide long-lasting and broad-spectrum immune protection for LAIVs 38 , our data suggest that dNS1-RBD has the potential to confer long-lasting protective immunity, particularly around the bronchoalveolar space and lungs.…”