Tissue-resident memory T (TRM) cells play a crucial role in local immunity by inducing rapid immune responses upon re-exposure of the antigen. However, how CD4+ TRM cells are retained in the skin after allergic inflammation remains largely unknown. To clarify the mechanism, we used a delayed-type hypersensitivity model, which is mediated by CD4+ T cells. T cell receptor (TCR)-β deficient mice were transferred with CD4+ T cells from GFP-expressing, ovalbumin (OVA)-specific TCR-transgenic (OT-II) mice and sensitized with OVA emulsion, followed by initial challenge with OVA in ear skin (day 0). On day 35, in spite of the resolution of ear swelling, CD4+ T cells remained in the dermis and exhibited CD44+CD69+ TRM cell phenotype. Their residency in the dermis was confirmed using parabiosis and photo-convertible protein (KikGR)-expressing OT-II T cells. In addition, two-photon microscopy revealed that CD4+ T cells were retained in perivascular clusters on day 35. Immunohistochemical analysis revealed that CD301b+ conventional dendritic cell (DC) subset 2 (cDC2) were colocalized with CD4+ T cells in the clusters. We selectively depleted these CD301b+ cells in Mgl2-diphtheria toxin receptor (DTR) mice, which express the DTR under the regulation of the gene encoding CD301b, and found that the number of CD4+ TRM cells and their clusters were reduced after the depletion of CD301b+ cells. Taken together, these results suggest that CD301b+ cDC2 cells are critical in the tissue residency of CD4+ TRM cells after the resolution of allergic inflammation. This mechanism provides a potential new strategy for preventing the recurrence of CD4+ T cell-mediated chronic inflammatory skin diseases.

ESDR001 - Maintenance of CD4+ tissue-resident memory T cells via perivascular clusters with CD301b+ dermal dendritic cells in a mouse model of allergic dermatitis

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING