Commensal-immune interactions

We have reported that a large proportion of human CD4+ T cells can acquire memory characteristics indicative of prior exposure even in the absence of known specific contact with the antigen. Yet it is unclear where these cells come from. Hypothesizing that pre-existing T cells retain the imprints from initial antigen engagement, we used trafficking molecules to gain insights into where this might have occurred for SARS-CoV-2-specific T cells from blood collected before the COVID-19 pandemic. We showed that pre-existing SARS-CoV-2-specific T cells from unexposed healthy adults expressed a variety of tissue tropic markers and could respond to gut and skin bacteria. We also found cross-reactivity with endemic circulating coronaviruses, but the responses to the microbiome were even more common! These data imply that exposure to commensal bacteria may help to drive the production of pre-existing SARS-CoV-2 specific CD4⁺ T cells. Is pre-existing memory helpful or harmful? Do pre-existing memory cells have a role in maintaining immune homeostasis with the environment? We are building on these findings to determine how basal microbial experiences shape responses to vaccines, infections, and autoimmunity.