Pathophysiology of Skin Resident Memory T Cells.

Tissue resident memory T (T) cells reside in peripheral, non-lymphoid tissues such as the skin, where they act as alarm-sensor cells or cytotoxic cells. Physiologically, skin T cells persist for a long term and can be reactivated upon reinfection with the same antigen, thus serving as peripheral sentinels in the immune surveillance network. CD8CD69CD103 T cells are the well-characterized subtype that develops in the epidermis. The local mediators such as interleukin (IL)-15 and transforming growth factor (TGF)-β are required for the formation of long-lived T cell population in skin. Skin T cells engage virus-infected cells, proliferate in response to local antigens and do not migrate out of the epidermis. Secondary T cell populations are derived from pre-existing T cells and newly recruited T precursors from the circulation. In addition to microbial pathogens, topical application of chemical allergen to skin causes delayed-type hypersensitivity and amplifies the number of antigen-specific CD8 T cells at challenged site. Skin T cells are also involved in the pathological conditions, including vitiligo, psoriasis, fixed drug eruption and cutaneous T-cell lymphoma (CTCL). The functions of these T cells seem to be different, depending on each pathology. Psoriasis plaques are seen in a recurrent manner especially at the originally affected sites. Upon stimulation of the skin of psoriasis patients, the CD8CD103CD49a T cells in the epidermis seem to be reactivated and initiate IL-17A production. Meanwhile, autoreactive CD8CD103CD49a T cells secreting interferon-γ are present in lesional vitiligo skin. Fixed drug eruption is another disease where skin T cells evoke its characteristic clinical appearance upon administration of a causative drug. Intraepidermal CD8 T cells with an effector-memory phenotype resident in the skin lesions of fixed drug eruption play a major contributing role in the development of localized tissue damage. CTCL develops primarily in the skin by a clonal expansion of a transformed T cells. CD8 CTCL with the pagetoid epidermotropic histology is considered to originate from epidermal CD8 T cells. This review will discuss the current understanding of skin T biology and their contribution to skin homeostasis and diseases.