Suppressive properties of human CD4+CD25+ regulatory T cells are dependent on CTLA-4 expression
Suppressive properties of human CD4+CD25+ regulatory T cells are dependent on CTLA-4 expression
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DOI：
10.1002/eji.200324632
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发表时间：
2004-12-01
影响因子：
5.4
通讯作者：
Semana, G
中科院分区：
文献类型：
--
作者：
Birebent, B;Lorho, R;Semana, G
已经证明，具有调节特性的T细胞存在于外周血CD 4（+）CD 25（+）T细胞区室中。在这里，我们描述了一种原始的方法，以纯化人的CD 4（+）CD 25（+）CD 152（+）T淋巴细胞作为活细胞，通过强制输出的CTLA-4分子储存在细胞表面的胞内囊泡。通过这样做，我们证明了CD 4（+）CD 25（+）T细胞含有一个更小和更均匀的群体，富含具有体外调节活性的细胞。此外，我们还发现，这种调节性T细胞的富集与Foxp 3表达的增加有关，并且CD 4（+）CD 25（+）CD 152（+）T淋巴细胞在控制同种异体抗原特异性T细胞的体外增殖方面显示出比平行纯化的CD 4（+）CD 25（+）CD 152（-）T淋巴细胞强得多的抑制活性。最后，通过纯化这些表达CTLA-4的细胞，我们证明了CTLA-4确实参与CD 4（+）CD 25（+）CD 152（+）T细胞调节活性，而抑制性细胞因子则不参与。
It has been demonstrated that T cells with regulatory properties are present within the peripheral blood CD4(+)CD25(+) T cell compartment. Here, we describe an original method to purify human CD4(+)CD25(+)CD152(+) T lymphocytes as living cells by forcing the exportation of CTLA-4 molecules stored in intracellular vesicules at the cell surface. By doing so, we demonstrate that CD4(+)CD25(+) T cells contain a smaller and more homogeneous population enriched in cells with in vitro regulatory activity. Moreover, we show that this enrichment in regulatory T cells is associated with an increased expression of Foxp3 and that CD4(+)CD25(+)CD152(+) T lymphocytes display a much stronger suppressive activity in controlling in vitro proliferation of alloantigen-specific T cells than CD4(+)CD25(+)CD152(-) T lymphocytes purified in parallel. Lastly, by purifying such cells expressing CTLA-4, we demonstrate that indeed CTLA-4 is involved in CD4(+)CD25(+)CD152(+) T cell regulatory activity, while suppressive cytokines are not.