Cross-reactive tissue-resident CD8⁺ T cells may provide first line of defence against SARS-CoV-2

Cross-reactive CD4⁺ T cells, likely induced by common cold coronavirus infections, are detected in 20–50% of peripheral blood samples from SARS-CoV-2 unexposed individuals. However, cross-reactive CD8⁺ T cells are rarely detected in these samples. To study whether this may be because CD8⁺ memory T cells are mostly located in tissues, Niessl at al. examined peripheral blood and tonsillar tissue samples from pre-2019. Indeed, they detected SARS-CoV-2 reactive CD8⁺ memory T cells in 32% of tissue samples. Cross-reactive CD4⁺ cells were detected at similar levels in blood and tissue, whereas cross-reactive memory CD8⁺ T cells were largely absent in matched blood samples. Tissue-resident cross-reactive CD8⁺ memory T cells displayed markers of follicular homing and tissue residency, and the authors speculate that these may enable rapid sentinel immune responses to SARS-CoV-2.