Spatial organization of tissue-resident memory T cells

Summary Tissue-resident memory T (TRM) cells durably reside in peripheral tissues, poised to deliver rapid local immune protection. TRM cells are found in most organs, and they are a core component of immunological memory, complementing circulating memory T cell populations. By definition, TRM cells can persist in tissues for months to years without antigen stimulation. However, demonstrating both residency and antigen absence in reality is challenging. Here, we discuss the strengths and challenges to our canonical definitions of TRM cells. We examine how early priming and subsequent tissue imprinting impact TRM cell programming. Finally, we underline the intra-tissue heterogeneity of TRM cells and provide a framework for resolving niche-level cues and refining TRM classification.