Gebhardt, T., Wakim, L.M., Eidsmo, L., Reading, P.C., Heath, W.R. & Carbone, F.R. Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus. Nat. Immunol. 10, 524-530

Department of Microbiology and Immunology, The University of Melbourne, Melbourne Victoria, Australia.
Nature Immunology (Impact Factor: 20). 04/2009; 10(5):524-30. DOI: 10.1038/ni.1718
Source: PubMed


Effective immunity is dependent on long-surviving memory T cells. Various memory subsets make distinct contributions to immune protection, especially in peripheral infection. It has been suggested that T cells in nonlymphoid tissues are important during local infection, although their relationship with populations in the circulation remains poorly defined. Here we describe a unique memory T cell subset present after acute infection with herpes simplex virus that remained resident in the skin and in latently infected sensory ganglia. These T cells were in disequilibrium with the circulating lymphocyte pool and controlled new infection with this virus. Thus, these cells represent an example of tissue-resident memory T cells that can provide protective immunity at points of pathogen entry.

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    • "In fact, cutaneous leukocyte antigen (CLA), CCR4, and CCR10 determines T cell cutaneous tropism (Sheridan and Lefrancois, 2011) and the large majority of CLA + lymphocytes reside in the skin (Clark et al., 2006). Importantly, the skin contains many resident T memory cells crucial in immunity against infections (Gebhardt et al., 2009; Wakim et al., 2008). In addition, the majors subsets of CD4 + T cells are present in particular Th1, Th2 and Th17, the latter know to play an important role against fungal and bacterial infections (Miossec et al., 2009). "
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    ABSTRACT: The porcine skin has striking similarities to the human skin in terms of general structure, thickness, hair follicle content, pigmentation, collagen and lipid composition. This has been the basis for numerous studies using the pig as a model for wound healing, transdermal delivery, dermal toxicology, radiation and UVB effects. Considering that the skin also represents an immune organ of utmost importance for health, immune cells present in the skin of the pig will be reviewed. The focus of this review is on dendritic cells, which play a central role in the skin immune system as they serve as sentinels in the skin, which offers a large surface area exposed to the environment. Based on a literature review and original data we propose a classification of porcine dendritic cell subsets in the skin corresponding to the subsets described in the human skin. The equivalent of the human CD141+ DC subset is CD1a−CD4−CD172a−CADM1high, that of the CD1c+ subset is CD1a+CD4−CD172a+CADM1+/low, and porcine plasmacytoid dendritic cells are CD1a−CD4+CD172a+CADM1−. CD209 and CD14 could represent markers of inflammatory monocyte-derived cells, either dendritic cells or macrophages. Future studies for example using transriptomic analysis of sorted populations are required to confirm the identity of these cells.
    Molecular Immunology 11/2014; 66(1). DOI:10.1016/j.molimm.2014.10.023 · 2.97 Impact Factor
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    • "This dichotomy is striking following herpes simplex virus infection (HSV) where antigen-specific CD4+ and CD8+ memory T cells localized to the dermis and epidermis, respectively, after clearance of the pathogen (18) (Figure 2A). The epidermal CD8+ T cells persist for long periods in this anatomical compartment (19) and are now commonly referred to as tissue-resident memory T cells (TRM). "
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    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.
    Frontiers in Immunology 07/2014; 5:332. DOI:10.3389/fimmu.2014.00332
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    • "Despite the relative juvenescence of the TRM field, the importance of this cell population has been alluded to for some time. TRM cells are positioned at the site of pathogen encounter as a front line of defense, and several studies have highlighted their role in defense against pathogenic challenges (7, 15–17). Indeed, in the case of influenza virus infection, the number of antigen-specific CD8+ T cells located within the respiratory tract correlates with the highest degree of heterosubtypic immunity (18, 19), and recently it has been shown that TRM specifically are responsible for this protection (20). "
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    ABSTRACT: Resident memory T cells (TRM) are broadly defined as a population of T cells, which persist in non-lymphoid sites long-term, do not re-enter the circulation, and are distinct from central memory T cells (TCM) and circulating effector memory T cells (TEM). Recent studies have described populations of TRM cells in the skin, gut, lungs, and nervous tissue. However, it is becoming increasingly clear that the specific environment in which the TRM reside can further refine their phenotypical and functional properties. Here, we focus on the TRM cells that develop following respiratory infection and reside in the lungs and the lung airways. Specifically, we will review recent studies that have described some of the requirements for establishment of TRM cells in these tissues, and the defining characteristics of TRM in the lungs and lung airways. With continual bombardment of the respiratory tract by both pathogenic and environmental antigens, dynamic fluctuations in the local milieu including homeostatic resources and niche restrictions can impact TRM longevity. Beyond a comprehensive characterization of lung TRM cells, special attention will be placed on studies, which have defined how the microenvironment of the lung influences memory T cell survival at this site. As memory T cell populations in the lung airways are requisite for protection yet wane numerically over time, developing a comprehensive picture of factors which may influence TRM development and persistence at these sites is important for improving T cell-based vaccine design.
    Frontiers in Immunology 07/2014; 5:320. DOI:10.3389/fimmu.2014.00320
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