Immunological memory and exhaustion are fundamental features of adaptive immunity. Recent advances reveal increasing heterogeneity and diversity among CD8 T-cell subsets, resulting in new subsets to annotate and understand. Here, we review our current knowledge of differentiation and maintenance of memory and exhausted CD8 T cells, including phenotypic classification, developmental paths, transcriptional and epigenetic features, and cell intrinsic and extrinsic factors. Additionally, we use this outline to discuss the nomenclature of effector, memory, and exhausted CD8 T cells. Finally, we discuss how new findings about these cell types may impact the therapeutic efficacy and development of immunotherapies targeting effector, memory, and/or exhausted CD8 T cells in chronic infections and cancer.
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