Another piece of the SARS-CoV-2 immunological response puzzle, here provided by a small study from Columbia/LJII/others (including Sette and Crotty).
They investigated T and B cell responses in naturally infected (deceased) organ donors. Findings were 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 for up to 6 months post-infection.
Importantly - the highest prevalence of SARS-CoV-2-specific memory T and B cells was found in the lungs and lung-associated lymph nodes, where they noted SARS-CoV-2-specific follicular helper T cells. Additionally,
SARS-CoV-2-specific germinal centres were active in those particular nodes for at least 6 months post-infection; there was evidence of ongoing germinal centre reactions following resolution of infection, consistent with other reports (cf vaccine thread posts, in particular previous findings of eg Nussenzweig
#1511). Additionally:
Germinal centre B cells were detected in donors spanning a broad age range - from 10-74 years, providing compelling evidence that the ability to establish robust germinal centre responses to novel pathogens can be maintained with age.
The low frequency of SARS-CoV-2-specific memory T or B cells found in the spleen suggested that virus infection is generally limited to mucosal sites of entry. Tissue localised and resident memory T and B cells in the lung are likely important for site-specific protection and could be targets for site-specific boosting in vaccination. This study demonstrates that the functional responses of virus-specific T cells are tissue-specific - not only at the site of infection, but also across numerous lymphoid tissues. This suggests that T cells in tissues mediate responses that are functionally adapted to the tissue site, resulting in heterogeneity of immune memory stored throughout the body.
They also found opposing/compensatory effects of humoral and cellular immune responses in lung-associated lymph nodes and lung tissue.
Further, results also indicated ongoing interaction and coordination between T and B cells within lymph nodes - findings which suggest that dynamic coordination of adaptive immune responses across the body is a feature of antiviral immunity to SARS-CoV-2.
Immune response and detail appears to be highly site specific within the body, which should be borne in mind when targeting vaccines and other treatments.
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.
In conclusion, we reveal here that immunological memory from SARS-CoV-2 infection is maintained as heterogeneous subsets across multiple sites, with active and preferential maintenance in lung and associated lymph nodes, as well as site-specific functional adaptations. These findings support the development of site-specific strategies for monitoring immune memory to infections and vaccines, and for fortifying immune responses at the infection sites.
DOI: 10.1126/sciimmunol.abl9105.