CD25+CD4+ regulatory T cells exert in vitro suppressive activity independent of CTLA-4
CD25+CD4+ regulatory T cells exert in vitro suppressive activity independent of CTLA-4
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DOI：
10.1093/intimm/dxh221
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发表时间：
2005-04-01
影响因子：
4.4
通讯作者：
Saito, T
中科院分区：
文献类型：
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作者：
Kataoka, H;Takahashi, S;Saito, T
细胞毒性T淋巴细胞抗原4（CTLA - 4）在CD25(+)CD4(+)调节性T细胞（Treg）上组成性表达，并被认为在Treg介导的抑制中起作用。然而，使用抗CTLA - 4进行分析的结果一直存在争议。我们通过分析CTLA - 4过表达或缺失的小鼠来解决这一问题。对于过表达，我们分析了表达CTLA - 4全长（FL）或截短（TL）突变体的CTLA - 4转基因小鼠。FL T细胞表达的CTLA - 4水平与Treg相似，而TL T细胞在细胞表面表达的水平要高得多。两种小鼠中Treg的数量均减少，尽管Foxp3的表达未改变。两种小鼠的Treg都具有抑制活性，而来自FL小鼠的CD25(-) T细胞没有抑制作用。此外，对年轻的CTLA - 4缺陷小鼠的CD25(+)CD4胸腺细胞进行分析，发现其具有抑制活性。这些结果表明，Treg在体外发挥抑制活性不依赖于CTLA - 4的表达。
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is constitutively expressed on CD25(+)CD4(+) regulatory T cells (Treg) and is suggested to play a role in Treg-mediated suppression. However, the results of analysis with anti-CTLA-4 have been controversial. We addressed this issue by analyzing mice over-expressing or deficient in CTLA-4. For over-expression, CTLA-4 transgenic mice expressing a full-length (FL) or a truncated (TL) mutant of CTLA-4 were analyzed. FL T cells expressed similar levels of CTLA-4 to Treg, whereas TL T cells expressed much higher levels on the cell surface. The number of Treg in both mice was decreased, although Foxp3 expression was not altered. Treg from both mice exerted suppressive activity, whereas CD25(-) T cells from FL mice showed no suppression. Furthermore, CD25(+)CD4 thymocytes from young CTLA-4-deficient mice were analyzed and found to exhibit suppressive activity. These results indicate that Treg exert in vitro suppressive activity independent of CTLA-4 expression.