人类CD8⁺CD25⁺胸腺细胞与CD4⁺CD25⁺调节性胸腺细胞具有共同的表型和功能特征。

Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes.

作者信息

Cosmi Lorenzo, Liotta Francesco, Lazzeri Elena, Francalanci Michela, Angeli Roberta, Mazzinghi Benedetta, Santarlasci Veronica, Manetti Roberto, Vanini Vittorio, Romagnani Paola, Maggi Enrico, Romagnani Sergio, Annunziato Francesco

机构信息

Dipartimento di Medicina Interna, Viale Morgagni 85, Firenze 50134, Italy.

出版信息

Blood. 2003 Dec 1;102(12):4107-14. doi: 10.1182/blood-2003-04-1320. Epub 2003 Jul 31.

DOI:10.1182/blood-2003-04-1320

PMID:12893750

Abstract

CD8+CD25+ cells, which expressed high levels of Foxp3, glucocorticoid-induced tumor necrosis factor receptor (GITR), CCR8, tumor necrosis factor receptor 2 (TNFR2), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) mRNAs, were identified in the fibrous septa and medullary areas of human thymus. Activated CD8+CD25+ thymocytes did not produce cytokines, but most of them expressed surface CTLA-4 and transforming growth factor beta1 (TGF-beta1). Like CD4+CD25+, CD8+CD25+ thymocytes suppressed the proliferation of autologous CD25-T cells via a contact-dependent mechanism. The suppressive activity of CD8+CD25+ thymocytes was abrogated by a mixture of anti-CTLA-4 and anti-TGF-beta1 antibodies and it was mediated by their ability to inhibit the expression of the interleukin 2 receptor alpha chain on target T cells. These results demonstrate the existence of a subset of human CD8+CD25+ thymocytes sharing phenotype, functional features, and mechanism of action with CD4+CD25+ T regulatory cells.

摘要

在人类胸腺的纤维间隔和髓质区域中，鉴定出了表达高水平叉头框蛋白3（Foxp3）、糖皮质激素诱导的肿瘤坏死因子受体（GITR）、CC趋化因子受体8（CCR8）、肿瘤坏死因子受体2（TNFR2）以及细胞毒性T淋巴细胞相关抗原4（CTLA-4）mRNA的CD8⁺CD25⁺细胞。活化的CD8⁺CD25⁺胸腺细胞不产生细胞因子，但它们中的大多数表达表面CTLA-4和转化生长因子β1（TGF-β1）。与CD4⁺CD25⁺细胞一样，CD8⁺CD25⁺胸腺细胞通过接触依赖性机制抑制自体CD25⁻T细胞的增殖。抗CTLA-4和抗TGF-β1抗体的混合物可消除CD8⁺CD25⁺胸腺细胞的抑制活性，并且其抑制活性是由它们抑制靶T细胞上白细胞介素2受体α链表达的能力介导的。这些结果证明，人类CD8⁺CD25⁺胸腺细胞亚群与CD4⁺CD25⁺调节性T细胞具有相同的表型、功能特征和作用机制。