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Review
. 2015 Jan 7;7(269):269rv1.
doi: 10.1126/scitranslmed.3010641.

Resident memory T cells in human health and disease

Rachael A Clark  1
Affiliations
Review

V体育官网入口 - Resident memory T cells in human health and disease

Rachael A Clark. Sci Transl Med. .

V体育官网 - Abstract

Resident memory T cells are non-recirculating memory T cells that persist long-term in epithelial barrier tissues, including the gastrointestinal tract, lung, skin, and reproductive tract VSports手机版. Resident memory T cells persist in the absence of antigens, have impressive effector functions, and provide rapid on-site immune protection against known pathogens in peripheral tissues. A fundamentally distinct gene expression program differentiates resident memory T cells from circulating T cells. Although these cells likely evolved to provide rapid immune protection against pathogens, autoreactive, aberrantly activated, and malignant resident memory cells contribute to numerous human inflammatory diseases including mycosis fungoides and psoriasis. This review will discuss both the science and medicine of resident memory T cells, exploring how these cells contribute to healthy immune function and discussing what is known about how these cells contribute to human inflammatory and autoimmune diseases. .

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Figures

Figure 1
Figure 1. Local skin infection leads to seeding of the entire skin surface with protective TRM
After a localized skin infection with vaccinia virus in mice, highly protective virus-specific TRM were generated that remained long term in the skin and provided local protection against reinfection (21). TRM were most numerous at the site of initial infection but these cells were also found in lower numbers in never infected skin. Note: Draft figures are shown. For professionally drawn figures, please see the published manuscript in Science Translational Medicine.
Figure 2
Figure 2. Local skin infection leads to protective TRM in other epithelial barrier tissues
After local skin infection with vaccinia virus in mice, protective TRM developed not only in the skin but also in lower numbers in the lungs and gastrointestinal tract (23, 24). Lung resident TRM induced by skin infection provided partial protection against an otherwise lethal pulmonary challenge with vaccinia. This protection was found to be mediated by early release of viral specific T cells proliferating in the skin draining lymph nodes after primary cutaneous infection. These T cells migrated to lymph nodes draining other tissues, proliferated in the absence of antigen and were imprinted with tropism for these distant tissues (23). Historical evidence suggests a similar biology exists in human beings. Smallpox vaccination, carried out by skin scarification with vaccinia virus, leads to protection against smallpox, an infection that is acquired via the respiratory route.
Figure 3
Figure 3. TRM are generated via a distinct, tissue induced differentiation program
Under conditions of both health and disease, antigens are transferred from the skin to the draining lymph nodes, where responding T cells are generated. A subset of these T cells home back to the skin and undergo a distinct TRM differentiation program that is induced only after entry into the peripheral tissues (1, 2). In the case of infectious pathogens, TRM provide rapid local immune protection against re-infection. However, the TRM program can also be engaged after exposure to allergens and auto-antigens and in these situations pathogenic TRM can be generated in peripheral tissues. In the skin, pathogenic TRM have been demonstrated in psoriasis and fixed drug eruption (–62).
Figure 4
Figure 4. TRM and skin-tropic TCM give rise to distinct inflammatory lesions in the skin
CTCL are a heterogeneous collection of lymphomas derived from skin tropic T cells. (A) In mycosis fungoides, a skin limited variant of CTCL, malignant T cells have the phenotype of TRM, do not recirculate and induce well demarcated stable inflammatory skin lesions that appear to resolve with topical therapies but often recur after treatment is discontinued (35, 56). (B) In contrast, patients with leukemic CTCL (L-CTCL) have malignant T cells that co-express both TCM markers (L-selectin, CCR7) and skin homing addressins (CLA, CCR4) (56). These T cells recirculate between the blood and skin (35), likely also enter lymph nodes and give rise to diffuse erythema of the skin.
Figure 5
Figure 5. TRM in human autoimmune, inflammatory and allergic disorders
Pathologic TRM have been directly demonstrated in psoriasis, mycosis fungoides and fixed drug eruption (shown in bold) but the clinical characteristics of many other human inflammatory diseases suggest a role for TRM. Clinical characteristics of TRM-mediated diseases include recurrent inflammation in the same anatomic locations, discrete, well demarcated inflammatory lesions, rapid onset of inflammation within 12 to 24 hours and progressively worsening disease with subsequent exposures.
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