Human circulating and tissue-resident memory CD8⁺ T cells

Our current knowledge of human memory CD8⁺ T cells is derived largely from studies of the intravascular space. However, emerging data are starting to challenge some of the dogmas based on this work, suggesting that a conceptual revision may be necessary. In this review, we provide a brief history of the field and summarize the biology of circulating and tissue-resident memory CD8⁺ T cells, which are ultimately responsible for effective immune surveillance. We also incorporate recent findings into a biologically integrated model of human memory CD8⁺ T cell differentiation. Finally, we address how future innovative human studies could improve our understanding of anatomically localized CD8⁺ T cells to inform the development of more effective immunotherapies and vaccines, the need for which has been emphasized by the global struggle to contain severe acute respiratory syndrome coronavirus 2.