Kubach Jan, Lutter Petra, Bopp Tobias, Stoll Sabine, Becker Christian, Huter Eva, Richter Christoph, Weingarten Petra, Warger Tobias, Knop Jürgen, Müllner Stefan, Wijdenes John, Schild Hansjörg, Schmitt Edgar, Jonuleit Helmut
Department of Dermatology, Johannes Gutenberg-University, Mainz, Germany.
Blood. 2007 Sep 1;110(5):1550-8. doi: 10.1182/blood-2007-01-069229. Epub 2007 May 14.
CD4(+)CD25(+)Foxp3(+) regulatory T cells (CD25(+) Treg cells) direct the maintenance of immunological self-tolerance by active suppression of autoaggressive T-cell populations. However, the molecules mediating the anergic state and regulatory function of CD25(+) Treg cells are still elusive. Using differential proteomics, we identified galectin-10, a member of the lectin family, as constitutively expressed in human CD25(+) Treg cells, while they are nearly absent in resting and activated CD4(+) T cells. These data were confirmed on the mRNA and protein levels. Single-cell staining and flow cytometry showed a strictly intracellular expression of galectin-10 in CD25(+) Treg cells. Specific inhibition of galectin-10 restored the proliferative capacity of CD25(+) Treg cells and abrogated their suppressive function. Notably, first identified here as expressed in human T lymphocytes, galectin-10 is essential for the functional properties of CD25(+) Treg cells.
CD4(+)CD25(+)Foxp3(+)调节性T细胞(CD25(+) Treg细胞)通过主动抑制自身攻击性T细胞群体来维持免疫自身耐受性。然而,介导CD25(+) Treg细胞无反应状态和调节功能的分子仍不清楚。利用差异蛋白质组学,我们鉴定出凝集素家族成员半乳糖凝集素-10在人CD25(+) Treg细胞中组成性表达,而在静息和活化的CD4(+) T细胞中几乎不存在。这些数据在mRNA和蛋白质水平上得到了证实。单细胞染色和流式细胞术显示半乳糖凝集素-10在CD25(+) Treg细胞中严格呈细胞内表达。对半乳糖凝集素-10的特异性抑制恢复了CD25(+) Treg细胞的增殖能力并消除了它们的抑制功能。值得注意的是,半乳糖凝集素-10首次在此被鉴定为在人T淋巴细胞中表达,它对CD25(+) Treg细胞的功能特性至关重要。