Tissue-resident T cells: dynamic players in skin immunity

Abstract

The skin is a large and complex organ that acts as a critical barrier protecting the body from pathogens in the environment. Numerous heterogeneous populations of immune cells are found within skin, including some that remain resident and others that can enter and exit the skin as part of their migration program. Pathogen-specific CD8(+) T cells that persist in the epidermis following infection are a unique population of memory cells with important roles in immune surveillance and protective responses to reinfection. How these tissue-resident memory T cells form in the skin, the signals controlling their persistence and behavior, and the mechanisms by which they mediate local recall responses are just beginning to be elucidated. Here, we discuss recent progress in understanding the roles of these skin-resident T cells and also highlight some of the key unanswered questions that need addressing.

Keywords: DETC; cell migration; intravital imaging; skin immunity; tissue-resident memory T cell; two-photon microscopy.

Figure 1

Skin structure and immune cell types found in skin. The skin is composed of epidermis and dermis, interspersed with hair follicles. Dead keratinocytes construct the stratum corneum in the outer epidermis. The dermis and epidermis are separated by a basement membrane. Blood vessels and lymphatic vessels and a network of fibroblasts are found in the dermis, as well as nerves, sebaceous glands, sweat glands (not shown). Multiple immune cells types are found within skin, including Langerhans cells, dendritic epidermal γδT cells (DETC), and memory αβT cells (T_RM) in the epidermis. In the steady state, the dermis contains a heterogeneous mix of immune cells, including subsets of dendritic cells (including CD11b⁺ and CD103⁺ DC), macrophages (including dermal and perivascular macrophages), neutrophils, mast cells, γδT cells, ILC, CD4⁺ T cells (both T_EM and possibly T_RM subsets), T regulatory cells (Treg), and CD8⁺ T_EM.

Figure 2

Tissue-resident immune cells in the epidermis. (A) CD4⁺ and CD8⁺ T cell localization in the skin of mice following clearance of HSV-1 infection. CD4⁺ T cells (red) localize to the dermis, while CD8⁺ T_RM persist in the epidermis. Nuclei are stained blue with DAPI. (B) Skin T_RM localize to the basal epidermis in contact with the basement membrane that separates dermis from epidermis. CD8⁺ T_RM, red; laminin-γ2, green; DAPI, blue. (C) The morphology of epidermis-resident T_RM, LC and DETC is distinct. Scale bars: A, B: 20 μm; C: 5 μm.