Figure 1.

Models of tissue memory diversity. (A) Establishment of tissue-resident memory T cells (Trm) at the site of infection/immunization. Trm precursor T cells (KLRG1⁻CX₃CR1⁻) recruited to the stroma receive tissue-derived instructive signals, including strong antigenic and inflammatory stimuli. Cells receiving appropriate instruction traffic through the basement membrane and differentiate into a unique population of epithelial Trm cells after receiving additional instructive cues. In the stroma, cells receive differential instructive stimuli and mature into diverse populations of Trm cells, such as the CD103⁺ and CD103⁻ subpopulations. Cells that did not receive any instructions do not up-regulate master transcription factors and leave the tissues as effector memory T cells (Tem). (B) Establishment of Trm cells at sites distal to infection/immunization sites. Basal levels of tissue instructive cues (e.g., TGF-β, IL-15, and aryl hydrocarbon receptor [AhR]) promote the establishment of quantitatively and qualitatively distinct populations of Trm cells as compared to their counterparts at the site of infection/immunization. In both cases, only cells in the blood are labeled by intravascular (i.v.) staining. (Ag) antigen, (DC) dendritic cell.