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Tissue‐resident memory T (TRM) cells are abundant in the memory T cell pool and remain resident in peripheral tissues, such as the skin, where they act as alarm sensors or cytotoxic killers. TRM cells persist long after the pathogen is eliminated and can respond rapidly upon reinfection with the same antigen. When aberrantly activated, skin‐located TRM cells have a profound role in various skin disorders, including vitiligo and melanoma. Autoreactive TRM cells are present in human lesional vitiligo skin and mouse models of vitiligo, which suggests that targeting these cells could be effective as a durable treatment strategy for vitiligo. Furthermore, emerging evidence indicates that induction of melanoma‐reactive TRM cells is needed to achieve effective protection against tumor growth. This review highlights seminal reports about skin‐resident T cells, focusing mainly on their role in the context of vitiligo and melanoma, as well as their potential as therapeutic targets in both diseases. [ABSTRACT FROM AUTHOR]

The health benefits of natural sunlight have been noted since the rise of civilization, even without the knowledge of its mechanisms of action. Currently, phototherapy remains an effective and widely used treatment for a variety of skin diseases. Ultraviolet radiation, from either the sun or artificial light sources, has a profound immunomodulatory effect that is responsible for its beneficial clinical outcomes. Ultraviolet radiation mostly induces the innate while suppressing the adaptive immune system, leading to both local and systemic effects. It is antigen specific, acts on both effector and regulatory T cells, alters antigen-presenting cell function, and induces the secretion of cytokines and soluble mediators. This review provides an overview of the immunologic mechanisms by which ultraviolet radiation is responsible for the therapeutic effects of phototherapy. [ABSTRACT FROM AUTHOR]

The article looks at a study regarding the phenotypically discrete populations of resident and recirculating memory T cells in human-engrafted mice and lymphoma patients using alemtuzumab. Topics discussed include epithelial barrier tissues are infiltrated by a combination of resident and recirculating T cells in mice, patients with cutaneous T cell lymphoma induced distinct inflammatory skin lesions and human skin is protected by four functionally distinct populations of T cells.

A substantial part of ongoing research in experimental dermatology focuses on skin T cells-for that reason, we find important to highlight the pioneering work of Jan D. Bos et al. from 1987 ( The skin immune system ( SIS ): Distribution and immunophenotype of lymphocyte subpopulations in normal skin) . This key article sets the record straight, once and for all, about the presence of lymphocytes in healthy skin, characterized the immunophenotypes of subpopulations, quantified these cells and studied their location. It was perhaps the critical discoveries made by Bos et al. that fuelled the scientific community's interest in skin lymphocytes, contributing to a new generation of cutaneous immunology research. We briefly describe additional scientific breakthroughs made since 1987. Nonetheless, the study of cutaneous lymphocytes remains essential to understand the relationship of these cells to human diseases and to develop therapies that can be leveraged to selectively mobilize, enhance or deplete these cells. [ABSTRACT FROM AUTHOR]

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT). Donor T cells are key mediators in pathogenesis, but a contribution from host T cells has not been explored, as conditioning regimens are believed to deplete host T cells. To evaluate a potential role for host T cells in GVHD, the origin of skin and blood T cells was assessed prospectively in patients after HSCT in the absence of GVHD. While blood contained primarily donor-derived T cells, most T cells in the skin were host derived. We next examined patient skin, colon, and blood during acute GVHD. Host T cells were present in all skin and colon acute GVHD specimens studied, yet were largely absent in blood. We observed acute skin GVHD in the presence of 100% host T cells. Analysis demonstrated that a subset of host T cells in peripheral tissues were proliferating (Ki67+) and producing the proinflammatory cytokines IFN-γ and IL-17 in situ. Comparatively, the majority of antigen-presenting cells (APCs) in tissue in acute GVHD were donor derived, and donor-derived APCs were observed directly adjacent to host T cells. A humanized mouse model demonstrated that host skin-resident T cells could be activated by donor monocytes to generate a GVHD-like dermatitis. Thus, host tissue-resident T cells may play a previously unappreciated pathogenic role in acute GVHD. [ABSTRACT FROM AUTHOR]

The development and maintenance of immune tolerance after allogeneic hematopoietic stemcell transplantation(HSCT) requires the balanced reconstitution of donor-derived CD4 regulatoryT cells (CD4Tregs) as well as effectorCD4 (conventionalCD4 T cells [CD4Tcons]) andCD8 T cells. To characterize the complex mechanisms that lead to unbalanced recovery of these distinct T-cell populations, we studied 107 adult patients who received T-replete stem cell grafts after reduced-intensity conditioning. Immune reconstitution of CD4Treg, CD4Tcon, and CD8 T cells was monitored for a 2-year period. CD3 T-cell counts gradually recovered to normal levels during this period but CD8 T cells recovered more rapidly than either CD4Tregs or CD4Tcons. Reconstituting CD4Tregs and CD4Tcons were predominantly central memory (CM) and effector memory (EM) cells and CD8 T cells were predominantly terminal EM cells. Thymic generation of naive CD4Tcon and CD8 T cells was maintained but thymic production ofCD4Tregswasmarkedly decreased with little recovery during the 2-year study. T-cell proliferation was skewed in favorofCMandEMCD4Tconand CD8 T cells, especially 6 to 12 months after HSCT. Intracellular expression of BCL2 was increased in CD4Tcon and CD8 T cells in the first 3 to 6 months after HSCT. Early recovery of naive and CM fractions within each T-cell population 3months after transplant was also strongly correlated with the subsequent development of chronic graft-versus-host disease (GVHD). These dynamic imbalances favor the production, expansion, and persistence of effector T cells over CD4Tregs and were associated with the development of chronic GVHD. [ABSTRACT FROM AUTHOR]