CD39 is involved in mediating suppression by Mycobacterium bovis BCG-activated human CD8+CD39+regulatory T cells

CD39 is involved in mediating suppression by Mycobacterium bovis BCG-activated human CD8+CD39+regulatory T cells
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DOI:
10.1002/eji.201243286
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发表时间:
2013-07-01
影响因子:
5.4
通讯作者:
Joosten, Simone A.
Joosten, Simone A.
中科院分区:
医学3区
文献类型:
--
作者:
Boer, Mardi C.;van Meijgaarden, Krista E.;Joosten, Simone A.

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调节性T(Treg)细胞可以通过限制炎性组织损伤来平衡正常组织稳态,例如在病原体感染期间,但另一方面也可以限制在自然感染期间或接种疫苗后诱导的保护性免疫。由于大多数研究都集中在CD 4(+)Treg细胞的作用上,因此对CD 8(+)Treg细胞的表型和功能知之甚少,特别是在感染性疾病中。在这里,我们首次描述了分枝杆菌激活的人CD 8(+)T细胞上的CD 39(E-NTPD酶1)的表达。这些CD 8(+)CD 39(+)T细胞显著共表达Treg标志物CD 25、Foxp 3、淋巴细胞活化基因-3(LAG-3)和CC趋化因子配体4(CCL 4),并抑制抗原特异性CD 4(+)T辅助细胞-1(Th 1)的增殖反应。药理学或抗体介导的CD 39功能阻断导致抑制的部分逆转。这些数据将CD 39鉴定为人类调节性CD 8(+)T细胞的新标志物,并表明CD 39在功能上参与CD 8(+)Treg细胞的抑制。
Regulatory T (Treg) cells can balance normal tissue homeostasis by limiting inflammatory tissue damage, e.g. during pathogen infection, but on the other hand can also limit protective immunity induced during natural infection or following vaccination. Because most studies have focused on the role of CD4(+) Treg cells, relatively little is known about the phenotype and function of CD8(+) Treg cells, particularly in infectious diseases. Here, we describe for the first time the expression of CD39 (E-NTPDase1) on Mycobacterium-activated human CD8(+) Tcells. These CD8(+)CD39(+) Tcells significantly co-expressed the Treg markers CD25, Foxp3, lymphocyte activation gene-3 (LAG-3), and CC chemokine ligand 4 (CCL4), and suppressed the proliferative response of antigen-specific CD4(+) T helper-1 (Th1) cells. Pharmacological or antibody mediated blocking of CD39 function resulted in partial reversal of suppression. These data identify CD39 as a novel marker of human regulatory CD8(+) Tcells and indicate that CD39 is functionally involved in suppression by CD8(+) Treg cells.