Pathophysiology of Skin Resident Memory T Cells
Y. Tokura, Pawit Phadungsaksawasdi, Kazuo Kurihara, Toshiharu Fujiyama, Tetsuya Honda
Abstract
Tissue resident memory T (T RM ) cells reside in peripheral, non-lymphoid tissues such as the skin, where they act as alarm-sensor cells or cytotoxic cells. Physiologically, skin T RM 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. CD8 + CD69 + CD103 + T RM 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 RM cell population in skin. Skin T RM cells engage virus-infected cells, proliferate in situ in response to local antigens and do not migrate out of the epidermis. Secondary T RM cell populations are derived from pre-existing T RM cells and newly recruited T RM 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 RM cells at challenged site. Skin T RM 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 RM 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 CD8 + CD103 + CD49a - T RM cells in the epidermis seem to be reactivated and initiate IL-17A production. Meanwhile, autoreactive CD8 + CD103 + CD49a + T RM cells secreting interferon-γ are present in lesional vitiligo skin. Fixed drug eruption is another disease where skin T RM cells evoke its characteristic clinical appearance upon administration of a causative drug. Intraepidermal CD8 + T RM 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 RM cells. CD8 + CTCL with the pagetoid epidermotropic histology is considered to originate from epidermal CD8 + T RM cells. This review will discuss the current understanding of skin T RM biology and their contribution to skin homeostasis and diseases.