Regulatory T cells – a brief history and perspective

Sakaguchi, Shimon; Wing, Kajsa; Miyara, Makoto

doi:10.1002/eji.200737593

Cited by 301 publications

(218 citation statements)

References 74 publications

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“…Increased levels of Tregs in the circulation and their presence in tumor tissue both are associated with poor survival in various malignancies, thus making them the focus of extensive research over the past decade. 8,9 The characteristic phenotype of Tregs is CD4-positive/CD25-positive/FOXP3-positive, and numerous publications have used FOXP3 (the most specific Treg marker to date) to identify tumorinfiltrating Tregs. 11,27,28 The clone of the monoclonal antibody 236A/E7, which was used in that work, previously underwent extensive evaluation, 11,29 and the results suggested strongly that the vast majority of detected In the current study, which was performed on a relatively large, continuous cohort with a long observation period, we demonstrated that the extent of COX-2 expression is of prognostic relevance for patients with UM.…”

Section: Discussionmentioning

confidence: 99%

“…Their immunosuppressive capability is critical for the prevention of autoimmune diseases; however, other than their involvement in autoimmunity, the role of Tregs in cancer immunology and especially tumor escape mechanisms increasingly is being recognized. 8 Several studies have demonstrated that Tregs promote tumor progression, and increased number of these immune suppressive lymphocytes have been detected in malignant lesions, sentinel lymph nodes, and peripheral blood from cancer patients in a variety of malignant diseases. 9 It is known that the number of Tregs correlates with disease prognosis, and increasing evidence indicates that tumor cells can recruit or induce Tregs directly or indirectly through the microenvironment.…”

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confidence: 99%

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Intratumoral forkhead box P3‐positive regulatory T cells predict poor survival in cyclooxygenase‐2–positive uveal melanoma

Mougiakakos

Johansson

Trocmé

et al. 2010

Cancer

115

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BACKGROUND: Forkhead box P3 (FOXP3)-positive regulatory T cells (Tregs) are key mediators of peripheral tolerance and suppress efficient antitumor responses. Prostaglandin E 2 (PGE 2 ) produced by inducible cyclooxygenase-2 (COX-2) can lead to Treg induction. COX-2 expression has been linked to tumorigenesis and growth in various malignancies. The objective of the current study was to investigate whether Tregs infiltrate uveal melanomas (UMs) and whether their prevalence is linked to COX-2 expression and the prediction of overall survival (OS). METHODS: One hundred patients who underwent enucleation after they were diagnosed with UM were included in the study. Immunohistochemical staining with monoclonal anti-FOXP3, anti-CD4, and anti-COX-2 antibodies was performed, and immunoreactivity was assessed. Correlations of COX-2 expression with the presence of Tregs, established clinicopathologic parameters, and OS were evaluated in univariate and multivariate analyses. RESULTS: High expression of COX-2 was predictive of shortened OS. FOXP3-positive Tregs were detectable in 24% of UMs and were restricted to malignant tissue. The extent of COX-2 expression was associated significantly with Treg prevalence (P ¼ .004) and Treg intratumoral localization (P ¼ .005). Intratumoral Tregs (but not the prevalence of Tregs) were independent marker for worse OS with a hazard ratio of 5.36 in patients with COX-2-positive tumors. CONCLUSIONS:The current results demonstrated that high COX-2 expression is associated with OS and Treg prevalence in UM. These findings are in line with the observations that COX-2/PGE 2 induces Tregs and that Tregs may alter antitumor responses, resulting in a negative effect on the clinical disease course. Intratumoral Tregs are an independent prognostic marker for COX

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Intratumoral forkhead box P3‐positive regulatory T cells predict poor survival in cyclooxygenase‐2–positive uveal melanoma

Mougiakakos

Johansson

Trocmé

et al. 2010

Cancer

115

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“…55 Finally the regulatory T-cells (Tregs) play a role in ILC and Th communication, 54 as well as helping to directly control Th response, which is particularly important in autoimmune dysfunction discussed later. 56 …”

Section: Respiratory Epithelial Cellsmentioning

confidence: 99%

Current prospects and future challenges for nasal vaccine delivery

Yusuf

Kett

2016

Human Vaccines & Immunotherapeutics

124

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Nasal delivery offers many benefits over traditional approaches to vaccine administration. These include ease of administration without needles that reduces issues associated with needlestick injuries and disposal. Additionally, this route offers easy access to a key part of the immune system that can stimulate other mucosal sites throughout the body. Increased acceptance of nasal vaccine products in both adults and children has led to a burgeoning pipeline of nasal delivery technology. Key challenges and opportunities for the future will include translating in vivo data to clinical outcomes. Particular focus should be brought to designing delivery strategies that take into account the broad range of diseases, populations and healthcare delivery settings that stand to benefit from this unique mucosal route. In this review the current state of the art in nasal vaccine delivery will be described along with future prospects. A brief introduction to the anatomy and physiology of the nasal cavity will highlight the advantages and disadvantages of the route. Encapsulation and presentation methods along with particular formulation considerations for the nasal route will also be discussed.There are many mucosal routes which have been regarded as potential sites for vaccine delivery such as oral, nasal, pulmonary, conjunctival, rectal and vaginal mucosa. However, for practical and cultural reasons researchers have tended to focus only on oral, nasal, and pulmonary administration. 1 Needlefree vaccines offer many advantages over traditional vaccination approaches including convenience, cost, ease of administration and disposal.There are several needle free methods of vaccination such as transdermal delivery and mucosal delivery. 2,3 Mucosal immunization has been successfully used in human vaccination. The human mucosal immune system is large and specialized in performing inspection for foreign antigens to protect the surfaces themselves and of course human body interior. Since most infections affect or start from mucosal surfaces, using a mucosal route of vaccination is of great interest and provides a rational reason to induce a protective immune response. 3 Nasal delivery of vaccine offers an easily accessible route to the immune system.The nose has the function of olfactory detection (sense of smell) and also filtration, humidification and temperature control of air as it enters the respiratory system. Moving from front to back the areas of the nasal cavity are the nasal vestibule, the respiratory region, and the olfactory region. The nasal cavity is divided by the septum to form the left and right nares, which lead into the left and right choana before opening onto the nasopharynx at the top of the throat. The turbinates bound the nasal walls and are responsible for air conditioning and the large mucosal surface area of the nasal cavity. The nose is also the main port of entry for many pathogens. The first barrier to foreign bodies is hair at the entrance to the nares, the nostrils, which successfully keeps ou...

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“…A dajkasejtekben ezek az éretlen sejtek még szaporodni is tudnak [10], miközben tovább differenciálódnak, azonban az autoreaktív T-lymphocyták túlnyomó többsége (mintegy 98%-a) elpusztul (negatív szelekció apoptózissal) és csak a maradék jut ki a perifériára az idegenfelismerő lym phocytákkal (pozitív szelekció) együtt. A perifériára kijutó autoreaktív T-sejteket az ugyancsak a thymusban fejlődő hosszú életű (úgynevezett természetes) regulátor (Treg-) sejtek ismerik fel, és bár nem ölik meg, gátolják a funkciókban (szuppresszor T-sejtek) [11]. A dajkasejtek felismerik és elpusztítják a degenerált T-lymphocytá-kat is [12], majd mind az autoreaktív, mind a degenerált T-lymphocytákat átadják a macrophagoknak, amelyek megemésztik azokat.…”

Section: A Thymus Immunszelekciós Működéseunclassified

A tobozmirigy-csecsemőmirigy rendszer szerepe az autoimmunitás, öregedés és élettartam szabályozásában

Csaba

2016

Orvosi Hetilap

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A csecsemőmirigy (thymus) immunoendokrin szerv, amelynek endokrin elemei által termelt hormonok elsősorban a szerv saját immunelemeire hatnak. Az immunrendszerben központi szerepet tölt be, újszülöttkori eltávolítása az immunrendszer és az egész szervezet összeomlásával jár. A thymus dajkasejtjei a csontvelő-eredetű lymphocytákat szelektálják és a sajátot idegenként felismerő (autoreaktív) sejteket még a thymusban elpusztítják, illetve az ugyancsak thymuseredetű Treg-sejtek a periférián elnyomják. A szerv involúciója már születés után elkezdődik, de csak a serdü-lőkor vége felé válik kifejezetté, mert addig az egyidejű fejlődési folyamatok túlkompenzálják. A pubertás utáni involúció inkább megengedi az autoreaktív sejtek életben maradását, felszaporodását és fokozott működését, ami fokozatosan koptatja, pusztítja a szervezet sejtjeit és sejt közötti állományát, ezzel előidézi az öregedés jelenségét. Az autoreaktív sejtek további fokozott működése okozza az autoimmun betegségeket és vezet a természetes halálhoz is. A thymus involúciója tehát nem a szervezet általános sorvadásának részjelensége, hanem annak okozója, ami az élettartam-pacemaker funkcióban mutatkozik meg. Az öregedés tehát felfogható egy thymusvezérelt lassú autoimmun folyamatnak. A tobozmirigy újszülöttkori eltávolítása a thymus degradációjához, az immunrendszer összeomlá-sához és a szervezet sorvadásához (wasting disease) vezet. A mirigy felnőttkori involúciója a thymus involúciójával párhuzamosan fut, így a két szerv funkcionális egységet képez. Valószínű, hogy a corpus pineale felelős a thymus involúciójáért, ezáltal annak élettartam-meghatározó szerepéért is. Az ismertetett adatok nem bizonyítják a tobozmirigy-csecsemőmirigy rendszer kizárólagos szerepét az öregedés és élettartam meghatározásában, csak felhívják a figyelmet arra, hogy ez a rendszer önmagában is alkalmas a feladat elvégzésére. Orv. Hetil., 2016, 157(27), 1065-1070. Kulcsszavak: tobozmirigy, csecsemőmirigy, öregedés, élettartam, immunitás, autoimmun betegségek, immunszelekció, immunöregedésThe role of the pineal-thymus system in the regulation of autoimmunity, aging and lifespan Thymus is an immunoendocrine organ, the hormones of which mainly influence its own lymphatic elements. It has a central role in the immune system, the neonatal removal causes the collapse of immune system and the whole organism. The thymic nurse cells select the bone marrow originated lymphocytes and destroy the autoreactive ones, while thymus originated Treg cells suppress the autoreactive cells in the periphery. The involution of the organ starts after birth, however, this truly happens in the end of puberty only, as before this it is overcompensated by developmental processes. From the end of adolescence the involution allows the life, proliferation and enhanced functioning of some autoreactive cells, which gradually wear down the cells and intercellular materials, causing the aging. The enhanced and mass function of autoreactive cells lead to the autoimmune diseases and natural death. This means that ...

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Regulatory T cells – a brief history and perspective

Cited by 301 publications

References 74 publications

Intratumoral forkhead box P3‐positive regulatory T cells predict poor survival in cyclooxygenase‐2–positive uveal melanoma

Intratumoral forkhead box P3‐positive regulatory T cells predict poor survival in cyclooxygenase‐2–positive uveal melanoma

Current prospects and future challenges for nasal vaccine delivery

A tobozmirigy-csecsemőmirigy rendszer szerepe az autoimmunitás, öregedés és élettartam szabályozásában

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