Figure 1.

Profile and function of T_RM cells. Left side: T_RM cells develop during primary infection. The differentiation and maintenance of T_RM cells is controlled by tissue-derived signals, e.g., TNF-α, TGF-β or IL-15 and IL-33 resulting in the up- and down-regulation of different genes via activity of the transcription factors Hobit, Blimp-1, Runx3, and Notch and the silencing of Klf2. In particular, upregulation of CD69 and CD103 and simultaneous downregulation of S1PR1 are key drivers of T_RM cell tissue retention. Other membrane molecules highly expressed in T_RM cells are CD49a, CD101, PD-1, CRTAM, and CXCR6 while CD62L, CCR7, and CX3CR1 show a decreased expression pattern in T_RM cells. Right side: After re-exposure to a cognate antigen (e.g., from a pathogen, shown in purple), T_RM cells are able to initiate a fast immune response. This includes chemokine release to recruit lymphocytes (indicated as red, orange, and blue immune cells) to the site of infection, release of pro-inflammatory cytokines (IFN-γ, TNF-α) to activate other cells as well as the production of the cytotoxic effectors perforin or granzyme B. There is also evidence for the ability of T_RM cells to proliferate or to re-differentiate (indicated as green and orange cells) and to leave the tissue (orange ex-T_RM cells; for details cf. main text). T_RM, tissue-resident memory T cell; TNF, tumor necrosis factor; TGF, transforming growth factor; IL, Interleukin; KLF, Krüppel-like factor; CD, cluster of differentiation; S1PR1, sphingosine-1-phosphate receptor 1; PD-1, programmed cell death protein 1; CRTAM, cytotoxic and regulatory T-cell molecule; CXCR, CXC-motif chemokine receptor; CCR, Chemokine receptor.