MHC class II expression identifies functionally distinct human regulatory T cells
MHC class II expression identifies functionally distinct human regulatory T cells
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DOI：
10.4049/jimmunol.176.8.4622
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发表时间：
2006-04-15
影响因子：
4.4
通讯作者：
Haller, David A.
中科院分区：
文献类型：
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作者：
Baecher-Allan, Clare;Wolf, Elizabeth;Haller, David A.
几十年来，人们已经知道循环中的人CD 4细胞可以表达功能性MHC II类分子，这些分子诱导T细胞对Ag呈递的无反应性。因为在亚群CD 4（+）CD 25（高）调节性T细胞（Treg）上存在MHC II类（MHC-II）决定簇（DR）的显著表达，我们检测了表达MHC-DR的CD 4细胞的功能。我们证明了在人CD 4（+）CD 25（高）高T细胞上的MHC-II表达鉴定了功能不同的Treg群体，其诱导早期接触，依赖性抑制与高Foxp 3表达相关。与此形成鲜明对比的是，MHC-II（-）CD 4（+）CD 25高Treg诱导早期IL-4和IL-10分泌以及晚期Foxp 3相关的接触依赖性抑制。与DR（-）CD 25（高）Treg群体相比，DR表达CD 25（高）Treg表达更高水平的Foxp 3信息和蛋白。CD 4（+）CD 25（高）Treg的直接单细胞克隆显示，无论初始DR表达如何，CD 25（高）而非DR的离体表达预测了哪些克隆将表现出接触依赖性抑制、高水平的Foxp 3信息和增加的成为DR表达组成型的倾向。因此，在CD 25（高）的情况下MHC-II的直接离体表达鉴定了参与接触依赖性体外抑制的成熟的、功能上不同的调节性T细胞群体。
It has been known for decades that circulating human CD4 cells can express functional MHC class II molecules that induce T cell nonresponsiveness with Ag presentation. Because there is significant expression of MHC class II (MHC-II) determinants (DR) on a subpopulation CD4(+)CD25(high) regulatory T cells (Treg), we examined the function of CD4 cells expressing MHC-DR. We demonstrate that MHC-II expression on human CD4(+)CD25(high) high T cells identifies a functionally distinct population of Treg that induces early contact-dependent suppression that is associated with high Foxp3 expression. In striking contrast, MHC-II(-)CD4(+)CD25 high Treg induce early IL-4 and IL-10 secretion and a late Foxp3-associated contact-dependent suppression. The DR expressing CD25(high) Treg express higher levels of Foxp3 message and protein, compared with the DR(-)CD25(high) Treg population. Direct single-cell cloning of CD4(+)CD25(high) Treg revealed that, regardless of initial DR expression, ex vivo expression of CD25(high), and not DR, predicted which clones would exhibit contact-dependent suppression, high levels of Foxp3 message, and an increased propensity to become constitutive for DR expression. Thus, the direct ex vivo expression of MHC-II in the context of CD25(high) identifies a mature, functionally distinct regulatory T cell population involved in contact-dependent in vitro suppression.