Figure 1.

Model of T_RM surveillance strategies according to organ topography. In epithelial barrier tissues such as epidermis, T_RM mainly locate on top of the basement membrane (BM) separating connective tissue from the epithelium, which themselves are connected by adherens and tight junctions. Both BM and tight junctions serve as physical boundaries to T_RM foraging, essentially restricting their motility to a 2D-like surface. Chemoattractants, either constitutively expressed or induced by microbial presence, together with α1 and αE integrins further re-enforce this restricted migration pattern to ensure long-term retention by preventing inadvertent loss of scanning T_RM outside the epithelial barrier. In exocrine glands such as the SMG (mixed arborized epithelial—connective tissue), tight junctions between secretory epithelial cells may constitute a similar barrier to prevent loss of T_RM into the acini or duct lumen. Yet, the BM separating secretory epithelium from supporting interstitium remains permissive for two-way traffic into and out of epithelial cell layers, which is facilitated in SMG by tissue macrophages. Accordingly, non-inflamed secretory epithelial cells presumably secrete only low levels of chemoattractants that would otherwise retain T_RM in this site. This mode of tissue scanning permits rapid accumulation of T_RM to sites of secondary pathogen encounters, which would be hampered if T_RM were confined exclusively to the epithelial cell layer. While CD69⁺ memory CD8⁺ cells also locate to lymphoid tissue following a viral infection (arrowheads), their function and dynamic interactions with local cells enabling their long-term retention and host protective capacity remain unknown. Similarly, it remains unclear whether SLO T_RM retain responsiveness to inflammatory chemokines as their counterparts in epithelial layers and exocrine glands. All confocal images show GFP⁺ OT-I CD8⁺ TCR transgenic T cells at >30 days following systemic or local (skin) virus infections. LSM, laser scanning microscope; SHG, second harmonic generation; LC, Langerhans cells; DC, Dendritic cells; BM, basement membrane, memT, CD8⁺ memory T cells. Scale bar LSM images, 30 μm. Middle panels created with https://biorender.com/.