Tissue-Resident Memory T Cells in Mice and Humans: Towards a Quantitative Ecology

In recent years, tissue-resident memory T cells (T_RM) have emerged as essential components of immunological memory. Following antigenic challenge, T_RM remain in nonlymphoid tissues and defend against re-exposure. Although accumulating evidence suggests important roles for T_RM in mediating protective immunity, fundamental aspects of the population biology of T_RM remain poorly understood. In this article, we discuss how results from different systems shed light on the ecological dynamics of T_RM in mice and humans. We highlight the importance of dissecting processes contributing to T_RM maintenance, and how these might vary across phenotypically and spatially heterogeneous subsets. We also discuss how the diversity of T_RM communities within specific tissues may evolve under competition and in response to antigenic perturbation. Throughout, we illustrate how mathematical models can clarify inferences obtained from experimental data and help elucidate the homeostatic mechanisms underpinning the ecology of T_RM populations.