Phenotype, localization, and mechanism of suppression of CD4(+)CD25(+) human thymocytes.
Phenotype, localization, and mechanism of suppression of CD4(+)CD25(+) human thymocytes.
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DOI：
10.1084/jem.20020110
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发表时间：
2002-08-05
期刊：
影响因子：
--
通讯作者：
Romagnani S
中科院分区：
文献类型：
--
作者：
Annunziato F;Cosmi L;Liotta F;Lazzeri E;Manetti R;Vanini V;Romagnani P;Maggi E;Romagnani S
研究了从出生后人胸腺中纯化的CD 4 + CD 25 + T细胞的表型标志物、定位、功能活性和体外作用机制。这些细胞在混合淋巴细胞培养（MLC）中表现出较差或无增殖，并以剂量依赖性方式抑制对同种异体刺激的CD 4 + CD 25 −胸腺细胞的增殖反应。几乎所有的CD 4 + CD 25+胸腺细胞组成型表达细胞质T淋巴细胞抗原（CTLA）-4，表面肿瘤坏死因子2型受体（TNFR 2）和CCR 8。它们主要定位于纤维间隔的血管周围区域，并对CCL 1/I-309的化学引诱活性作出反应，发现CCL 1/I-309由胸腺髓质巨噬细胞或纤维间隔上皮细胞产生。经多克隆活化后，CD 4 + CD 25+胸腺细胞不产生细胞因子白细胞介素（IL）-2，IL-4，IL-5，IL-13，干扰素γ，只有极少数产生IL-10，但它们都在其表面表达CTLA-4，大多数还表达转化生长因子（TGF）-β1。这些细胞的抑制活性是接触依赖性的，并且与靶细胞中缺乏IL-2受体（IL-2 R）α链（CD 25）表达相关。这种抑制活性被抗CTLA-4或抗TGF-β1部分抑制，并被这些单克隆抗体的混合物完全阻断，这些单克隆抗体也能够恢复靶T细胞中IL-2 R α链的表达，因此恢复其对IL-2的反应性。这些数据表明，CD 4 + CD 25+人胸腺细胞代表一群调节细胞，其响应趋化因子CCL 1/I-309而迁移，并通过抑制靶T细胞中的IL-2 R α链（由CTLA-4和膜TGF-β1的联合活性诱导）发挥其抑制功能。
Phenotypic markers, localization, functional activities, and mechanisms of action in vitro of CD4+CD25+ T cells, purified from postnatal human thymuses, were investigated. These cells showed poor or no proliferation in mixed lymphocyte culture (MLC), and suppressed in a dose-dependent fashion the proliferative response to allogeneic stimulation of CD4+CD25− thymocytes. Virtually all CD4+CD25+ thymocytes constitutively expressed cytoplasmic T lymphocyte antigen (CTLA)-4, surface tumor necrosis factor type 2 receptor (TNFR2), and CCR8. They prevalently localized to perivascular areas of fibrous septa and responded to the chemoattractant activity of CCL1/I-309, which was found to be produced by either thymic medullary macrophages or fibrous septa epithelial cells. After polyclonal activation, CD4+CD25+ thymocytes did not produce the cytokines interleukin (IL)-2, IL-4, IL-5, IL-13, interferon γ, and only a very few produced IL-10, but all they expressed on their surface CTLA-4 and the majority of them also transforming growth factor (TGF)-β1. The suppressive activity of these cells was contact dependent and associated with the lack of IL-2 receptor (IL-2R) α-chain (CD25) expression in target cells. Such a suppressive activity was partially inhibited by either anti–CTLA-4 or anti–TGF-β1, and was completely blocked by a mixture of these monoclonal antibodies, which were also able to restore in target T cells the expression of IL-2R α-chain and, therefore, their responsiveness to IL-2. These data demonstrate that CD4+CD25+ human thymocytes represent a population of regulatory cells that migrate in response to the chemokine CCL1/I-309 and exert their suppressive function via the inhibition of IL-2R α-chain in target T cells, induced by the combined activity of CTLA-4 and membrane TGF-β1.
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DOI：
10.1084/jem.193.11.1303
发表时间：
2001-06-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dieckmann D;Plottner H;Berchtold S;Berger T;Schuler G
通讯作者：
Schuler G
人CD25（+）CD4（+）T调节细胞抑制幼稚和记忆T细胞增殖，可以在体外扩展而不会失去功能。
影响因子：
15.3
作者：
Levings, M K;Sangregorio, R;Roncarolo, M G
通讯作者：
Roncarolo, M G
DOI：
10.1084/jem.194.6.847
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Iellem A;Mariani M;Lang R;Recalde H;Panina-Bordignon P;Sinigaglia F;D'Ambrosio D
通讯作者：
D'Ambrosio D
影响因子：
5.5
作者：
GIRI, JG;ANDERSON, DM;COSMAN, D
通讯作者：
COSMAN, D
影响因子：
20.3
作者：
Romagnani, P;Annunziato, F;Romagnani, S
通讯作者：
Romagnani, S