Human and Mouse CD8(+)CD25(+)FOXP3(+) Regulatory T Cells at Steady State and during Interleukin-2 Therapy.
Human and Mouse CD8(+)CD25(+)FOXP3(+) Regulatory T Cells at Steady State and during Interleukin-2 Therapy.
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DOI：
10.3389/fimmu.2015.00171
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发表时间：
2015
影响因子：
7.3
通讯作者：
Klatzmann D
中科院分区：
文献类型：
--
作者：
Churlaud G;Pitoiset F;Jebbawi F;Lorenzon R;Bellier B;Rosenzwajg M;Klatzmann D
除了CD 4+调节性T细胞（TCD 4）之外，CD 8+抑制性T细胞正在成为调节性T细胞的重要亚群。已经描述了具有抑制活性的CD 8 + T细胞的不同群体。其中，在小鼠和人类中都发现了少量的CD 8 + CD 25 + FOXP 3 + T细胞。与胸腺来源的CD 4 + CD 25 + FOXP 3 + T细胞相比，它们的起源及其在自身免疫性疾病（AIDS）病理生理学中的作用尚不清楚。我们在这里报告的数量，表型和功能的CD 8 + T细胞在小鼠和人类，在稳定状态和低剂量白细胞介素-2（IL-2）的反应。CD 8 + T细胞分别占健康人和小鼠外周血T细胞的约0.4%和0.1%。在小鼠中，它们在淋巴结（LN）和脾脏中的频率非常相似，但在派尔集合淋巴结和肠系膜淋巴结中的频率要高出两到三倍。CD 8 + T细胞表达低水平的CD 127。与其他CD 8 + T细胞相比，CD 8 + Treg表达更多的激活或增殖标志物，例如CTLA-4、ICOS和Ki-67。在体外，它们抑制效应T细胞增殖以及或甚至优于CD 4 + T细胞。由于CD 25的组成性表达，CD 8 + T细胞对体外IL-2刺激的敏感性比CD 8+效应T细胞高20- 40倍，但比CD 4 + T细胞低2-4倍。然而，在小鼠和人中，低剂量IL-2显著扩增和激活CD 8 + T细胞，甚至比CD 4 + T细胞更多。进一步的研究是必要的，以充分了解CD 8 + T细胞在艾滋病的临床相关性和IL-2治疗的疗效。
In addition to CD4+ regulatory T cells (Tregs), CD8+ suppressor T cells are emerging as an important subset of regulatory T cells. Diverse populations of CD8+ T cells with suppressive activities have been described. Among them, a small population of CD8+CD25+FOXP3+ T cells is found both in mice and humans. In contrast to thymic-derived CD4+CD25+FOXP3+ Tregs, their origin and their role in the pathophysiology of autoimmune diseases (AIDs) are less understood. We report here the number, phenotype, and function of CD8+ Tregs cells in mice and humans, at the steady state and in response to low-dose interleukin-2 (IL-2). CD8+ Tregs represent approximately 0.4 and 0.1% of peripheral blood T cells in healthy humans and mice, respectively. In mice, their frequencies are quite similar in lymph nodes (LNs) and the spleen, but two to threefold higher in Peyer patches and mesenteric LNs. CD8+ Tregs express low levels of CD127. CD8+ Tregs express more activation or proliferation markers such as CTLA-4, ICOS, and Ki-67 than other CD8+ T cells. In vitro, they suppress effector T cell proliferation as well as or even better than CD4+ Tregs. Owing to constitutive expression of CD25, CD8+ Tregs are 20- to 40-fold more sensitive to in vitro IL-2 stimulation than CD8+ effector T cells, but 2–4 times less than CD4+ Tregs. Nevertheless, low-dose IL-2 dramatically expands and activates CD8+ Tregs even more than CD4+ Tregs, in mice and humans. Further studies are warranted to fully appreciate the clinical relevance of CD8+ Tregs in AIDs and the efficacy of IL-2 treatment.
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DOI：
10.1111/j.1600-6143.2012.04133.x
发表时间：
2012-09
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Aoyama A;Klarin D;Yamada Y;Boskovic S;Nadazdin O;Kawai K;Schoenfeld D;Madsen JC;Cosimi AB;Benichou G;Kawai T
通讯作者：
Kawai T
影响因子：
11.2
作者：
Correale, Jorge;Villa, Andres
通讯作者：
Villa, Andres
影响因子：
4.4
作者：
Brimnes, J;Allez, M;Mayer, L
通讯作者：
Mayer, L
影响因子：
14.2
作者：
Allakhverdi, Zoulfia;Fitzpatrick, David;Delespesse, Guy
通讯作者：
Delespesse, Guy
影响因子：
4.4
作者：
Filaci, G;Bacilieri, S;Indiveri, F
通讯作者：
Indiveri, F