Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood.
Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood.
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DOI：
10.1084/jem.193.11.1303
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发表时间：
2001-06-04
期刊：
影响因子：
--
通讯作者：
Schuler G
中科院分区：
文献类型：
--
作者：
Dieckmann D;Plottner H;Berchtold S;Berger T;Schuler G
多年来人们已知啮齿动物体内存在一种独特的CD4 + CD25 +“专职”调节/抑制性T细胞群，它对预防自发性自身免疫疾病至关重要。在此我们证明，成年健康志愿者血液中存在CD4 + CD25 + CD45RO + T细胞（平均占CD4 + T细胞的6%）。与先前的报道不同，这些CD4 + CD25 + T细胞并非传统的记忆细胞，而是表现出与啮齿动物同类细胞相同特性的调节细胞。例如，细胞毒性T淋巴细胞相关抗原（CTLA）-4（CD152），它对CD4 + CD25 + T细胞的体内抑制活性至关重要，是组成性表达的，并且在刺激后仍强烈上调。这些细胞在通过其抗原T细胞受体受到刺激时不增殖，但无反应状态可被白细胞介素（IL）-2和IL - 15部分逆转。在用同种异体（而非同基因）成熟树突状细胞或板结合的抗CD3加抗CD28刺激时，CD4 + CD25 + T细胞释放IL - 10，并且在共培养实验中抑制了CD4 +和CD8 + T细胞的活化和增殖。已证明这种抑制作用不依赖于IL - 10，但与在小鼠中一样是接触依赖性的。调节性CD4 + CD25 + T细胞的鉴定对人类耐受性的研究具有重要意义，特别是在自身免疫、移植和癌症的背景下。
It has been known for years that rodents harbor a unique population of CD4+CD25+ “professional” regulatory/suppressor T cells that is crucial for the prevention of spontaneous autoimmune diseases. Here we demonstrate that CD4+CD25+CD45RO+ T cells (mean 6% of CD4+ T cells) are present in the blood of adult healthy volunteers. In contrast to previous reports, these CD4+CD25+ T cells do not constitute conventional memory cells but rather regulatory cells exhibiting properties identical to their rodent counterparts. Cytotoxic T lymphocyte–associated antigen (CTLA)-4 (CD152), for example, which is essential for the in vivo suppressive activity of CD4+CD25+ T cells, was constitutively expressed, and remained strongly upregulated after stimulation. The cells were nonproliferative to stimulation via their T cell receptor for antigen, but the anergic state was partially reversed by interleukin (IL)-2 and IL-15. Upon stimulation with allogeneic (but not syngeneic) mature dendritic cells or platebound anti-CD3 plus anti-CD28 the CD4+CD25+ T cells released IL-10, and in coculture experiments suppressed the activation and proliferation of CD4+ and CD8+ T cells. Suppression proved IL-10 independent, yet contact dependent as in the mouse. The identification of regulatory CD4+CD25+ T cells has important implications for the study of tolerance in man, notably in the context of autoimmunity, transplantation, and cancer.
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DOI：
10.1016/0090-1229(90)90012-f
发表时间：
1990-01-01
期刊：
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY
影响因子：
--
作者：
JACKSON, AL;MATSUMOTO, H;SHYE, S
通讯作者：
SHYE, S
影响因子：
15.3
作者：
Roncarolo, M G;Levings, M K;Traversari, C
通讯作者：
Traversari, C
影响因子：
4.4
作者：
Takahashi, T;Kuniyasu, Y;Sakaguchi, S
通讯作者：
Sakaguchi, S
DOI：
10.1084/jem.192.9.1213
发表时间：
2000-11-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jonuleit H;Schmitt E;Schuler G;Knop J;Enk AH
通讯作者：
Enk AH
影响因子：
32.4
作者：
Salomon, B;Lenschow, DJ;Bluestone, JA
通讯作者：
Bluestone, JA