Location, location, location: Tissue resident memory T cells in mice and humans

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Science Immunology  05 Apr 2019:
Vol. 4, Issue 34, eaas9673
DOI: 10.1126/sciimmunol.aas9673


  • Fig. 1 Approaches for the study of TRM in mice and humans.

    (A) Parabiosis. Parabiotic surgery, shown here as the conjoining of the skin between two congenic mice, results in anastomosis of the vasculature, enabling assessment of in vivo circulatory potential. TRM (generated by previous infection in one of the mice) fail to equilibrate between parabionts, providing evidence for tissue residency. (B) In vivo antibody labeling. Intravascular injection of fluorescently labeled or depleting antibodies targets cells in vascular compartments, leaving those outside of the circulation (within the tissue parenchyma) protected from antibody labeling. (C) Tissue transplantation. Analysis of donor and recipient T cells within transplanted organs and tissues allows assessment of retention of donor T cells within (and outside) the graft and influx of recipient cells from circulation. (D) Cell phenotype and transcriptional profile. Expression of CD69, CD103, and other TRM accessory markers (Table 1) by means of flow cytometry is frequently used to define TRM in human tissues or mouse models of infection. Transcriptional profiling [such as microarray or RNA sequencing (RNA-seq)] has been used to define gene signatures and TFs associated with tissue residency.

  • Fig. 2 TRM compartmentalization and tissue niches in mice and humans.

    Noncirculating TRM take up residence in distinct mucosal, lymphoid, and barrier sites throughout mice and human tissues. Percentages in each tissue denote the frequency of T cells that exhibit surface markers indicating residency (CD69+CD103+/−) in both humans and mouse models of infection (for references, see text). (Top) In mice, CD103+CD8+ TRM accumulate within the lung epithelium or areas of tissue injury and are maintained by DCs producing TGF-β. CD4+ TRM localize around B cell follicles. In humans, CD103+CD8+ TRM accumulate in the epithelium, and CD103CD4+ TRM are common in the lamina propria. (Middle) LN TRM are infrequent in conventional specific pathogen–free mice, lack CD103, and reside primarily near the subcapsular sinus. LN CD4+ and CD8+ TRM in humans are more abundant as compared with mice. (Bottom) CD103+CD8+ TRM in previously infected mice are the most prevalent skin TRM population, reside in the epidermis, and are maintained by IL-7, IL-5, and TGF-β signals. A proportion of CD4+ T cells expressing CD69 in the dermis retain their ability to recirculate. In humans, dermal CD103CD4+ TRM are the most prevalent population, whereas CD103+CD8+ TRM predominate in the epidermis.



  • Table 1 A comparison between mouse and human TRM.

    Ab, antibody; SG, salivary gland.

    Techniques to define tissue residencyParabiosis (7, 12, 3941), in vivo labeling
    (7, 8, 11, 46), Ab depletion (10, 47, 48), FTY720
    (11, 4952), transplantation (46, 53), and
    transcriptional profiling (1315, 32, 83).
    Transcriptional profiling (18, 22, 23, 32, 33, 71, 93),
    Ab depletion (54), and transplantation (5557).
    Canonical phenotypeCD69+CD103+/−CD69+CD103+/−
    Accessory markersCD101, CD49a, PD-1, CXCR6, CLA, LFA1, CD11a,
    CXCR3, and CCR10 (7, 14, 53, 69, 78, 89).
    CD101, CD49a, PD-1, CXCR6, CLA, and CCR8
    (18, 27, 32, 33, 74, 93, 94).
    TFsHobit and Blimp1 (13), Runx3 for CD8+ TRM (83),
    and Notch for CD103+CD8+ TRM maintenance (32).
    Hobit, Blimp1, and Runx3 (18, 33) and Notch/RBPj
    enriched on lung TRM (32, 33, 57)
    Tissue maintenanceMaintained over months: skin (12, 91), gut (6),
    brain (64), lung (CD4+ TRM) (11, 48), liver (89), and
    SG (108). Wane over months: lung CD8+ TRM (91).
    Maintained over years: skin (56), intestine (55), and
    lung (57). TRM frequency maintained over life
    (17, 24).
    Features in nonlymphoid tissuesSkin CD103+/−CD4+ TRM most frequent in naïve
    mice (45); epidermal CD103+CD8+ TRM and dermal
    CD103+/−CD4+ TRM accrue in infected mice (65).
    Liver CD8+ TRM lack CD103 (89).
    Epidermal CD103+CD4+ TRM and dermal
    CD103CD4+ TRM most frequent in healthy skin
    (66). Liver CD8+ TRM express CD103 (27).
    Features in lymphoid tissuesLN CD8+ TRM infrequent (40), more abundant in
    dirty mice (38). BM CD8+ T cells recirculate (39).
    Large TRM pool (18, 22, 71) and LN-specific
    transcriptional profile (22). BM CD69+CD4+ T cells
    quiescent, broad specificities (26).
    Role in immunityProtective in viral (5, 7, 43, 90), bacterial
    (49, 67, 73, 104, 107), parasitic (89), and fungal (106)
    Correlation of antigen-specific TRM abundance to
    viral control (27, 71, 113).
    Potential target for vaccinationDemonstrable (50, 52, 89, 98, 119124)Promising

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