Mesenchymal stem cell effects on T-cell effector pathways.
Mesenchymal stem cell effects on T-cell effector pathways.
复制标题
DOI：
10.1186/scrt75
复制
发表时间：
2011-08-11
影响因子：
7.5
通讯作者：
Griffin MD
中科院分区：
文献类型：
--
作者：
Duffy MM;Ritter T;Ceredig R;Griffin MD
间充质干细胞（Mesenchymal stem cells，MSCs）是一种罕见的多能祖细胞，可以从骨髓和其他组织中分离和扩增。引人注目的是，MSC调节免疫细胞的功能，包括T细胞、B细胞、自然杀伤细胞、单核细胞/巨噬细胞、树突细胞和嗜中性粒细胞。T细胞被激活以执行一系列不同的效应器功能，是许多自身免疫性和炎性疾病以及移植排斥和移植物抗宿主病的主要介质。明确定义的T细胞效应表型包括CD 4+（T辅助细胞）亚群Th 1、Th 2和Th 17细胞以及来源于幼稚CD 8+前体抗原特异性活化的细胞毒性T淋巴细胞。此外，天然存在的和诱导的调节性T细胞（Treg）代表CD 4+和CD 8 + T细胞表型，其有效地抑制效应T细胞以防止自身免疫，维持自身耐受性，并限制炎性组织损伤。许多免疫介导的疾病需要Treg和一种或多种表型的效应T细胞之间的不平衡。MSC通过大量的可溶性和细胞接触依赖性介质广泛抑制体外T细胞活化和增殖。这些介质可以直接作用于T细胞或通过调节抗原呈递细胞和其他辅助细胞间接作用于T细胞。MSC给药也已被证明与自身免疫和移植模型以及几项人类临床试验中的有益作用密切相关。然而，在少数研究中，发现MSC给药会加重T细胞介导的组织损伤。MSC对细胞免疫的多重作用可能反映了它们对不同T细胞效应子亚群的不同影响及其特异性保护或诱导Treg群体的能力。在这篇综述中，我们专注于从最近的文献中，骨髓间充质干细胞对一个或多个单独的效应T细胞亚群和调节性T细胞表型的特定调节作用的研究结果在体外，在相关的动物模型，在体内免疫疾病，并在人类受试者。我们的结论是，骨髓间充质干细胞有可能直接或间接抑制疾病相关的Th 1，Th 2和Th 17细胞以及细胞毒性T淋巴细胞，但许多关键问题的效力，特异性，机制基础，这些调节作用的可预测的治疗价值仍然没有答案。
Mesenchymal stem (stromal) cells (MSCs) are rare, multipotent progenitor cells that can be isolated and expanded from bone marrow and other tissues. Strikingly, MSCs modulate the functions of immune cells, including T cells, B cells, natural killer cells, monocyte/macrophages, dendritic cells, and neutrophils. T cells, activated to perform a range of different effector functions, are the primary mediators of many autoimmune and inflammatory diseases as well as of transplant rejection and graft-versus-host disease. Well-defined T-cell effector phenotypes include the CD4+ (T helper cell) subsets Th1, Th2, and Th17 cells and cytotoxic T lymphocytes derived from antigen-specific activation of naïve CD8+ precursors. In addition, naturally occurring and induced regulatory T cells (Treg) represent CD4+ and CD8+ T-cell phenotypes that potently suppress effector T cells to prevent autoimmunity, maintain self-tolerance, and limit inflammatory tissue injury. Many immune-mediated diseases entail an imbalance between Treg and effector T cells of one or more phenotypes. MSCs broadly suppress T-cell activation and proliferation in vitro via a plethora of soluble and cell contact-dependent mediators. These mediators may act directly upon T cells or indirectly via modulation of antigen-presenting cells and other accessory cells. MSC administration has also been shown to be variably associated with beneficial effects in autoimmune and transplant models as well as in several human clinical trials. In a small number of studies, however, MSC administration has been found to aggravate T cell-mediated tissue injury. The multiple effects of MSCs on cellular immunity may reflect their diverse influences on the different T-cell effector subpopulations and their capacity to specifically protect or induce Treg populations. In this review, we focus on findings from the recent literature in which specific modulatory effects of MSCs on one or more individual effector T-cell subsets and Treg phenotypes have been examined in vitro, in relevant animal models of in vivo immunological disease, and in human subjects. We conclude that MSCs have the potential to directly or indirectly inhibit disease-associated Th1, Th2, and Th17 cells as well as cytotoxic T lymphocytes but that many key questions regarding the potency, specificity, mechanistic basis, and predictable therapeutic value of these modulatory effects remain unanswered.
登录
查看更多内容
影响因子：
13.6
作者：
Ankrum J;Karp JM
通讯作者：
Karp JM
DOI：
10.4049/jimmunol.0900803
发表时间：
2009-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Fiorina P;Jurewicz M;Augello A;Vergani A;Dada S;La Rosa S;Selig M;Godwin J;Law K;Placidi C;Smith RN;Capella C;Rodig S;Adra CN;Atkinson M;Sayegh MH;Abdi R
通讯作者：
Abdi R
影响因子：
2.6
作者：
Bartholomew, A;Sturgeon, C;Hoffman, R
通讯作者：
Hoffman, R
影响因子：
4.4
作者：
Cutler, Antony J.;Limbani, Vasanti;Navarrete, Cristina V.
通讯作者：
Navarrete, Cristina V.
影响因子：
4.6
作者：
English, K.;Ryan, J. M.;Mahon, B. P.
通讯作者：
Mahon, B. P.