Origins of CD8 tissue resident memory

The concept that immune cells, specifically T cells, become established and reside in peripheral tissues, especially at barrier sites, has been around for several decades. Recent studies have revealed substantial heterogeneity at the cellular level that depends on the type of immune response and tissue environment, among many other factors. Nevertheless, some features are common to most resident memory T cells, especially CD8+ cells. These include certain surface receptors and transcription factors. It is important to understand how tissue-resident memory (T_RM) T cells develop and function, as these cells are critical for subsequent protective immune responses when the same or antigenically drifted variants of a pathogen are encountered. CD8+ T cells resembling T_RM can be found in solid tumors and correlate with prognosis. It is attractive to consider devising strategies to generate T_RM for preventive or therapeutic interventions. While there is information on how resident memory T cells develop, our understanding is incomplete, and many questions remain. Here, we review the origins and early observations on the concept of memory T cell residency, models of how and where resident memory forms, and the open questions that remain.