Acquisition of suppressive function by activated human CD4+ CD25- T cells is associated with the expression of CTLA-4 not FoxP3.
Acquisition of suppressive function by activated human CD4+ CD25- T cells is associated with the expression of CTLA-4 not FoxP3.
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DOI：
10.4049/jimmunol.181.3.1683
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发表时间：
2008-08-01
期刊：
影响因子：
--
通讯作者：
Sansom DM
中科院分区：
文献类型：
--
作者：
Zheng Y;Manzotti CN;Burke F;Dussably L;Qureshi O;Walker LS;Sansom DM
CTLA-4在调节性T细胞（Treg）功能中的作用尚未完全了解。我们已经研究了CTLA-4的作用及其与转录因子FoxP 3的关系，在人外周血中使用Treg诱导模型。人CD 4 + CD 25- T细胞的活化导致在48小时内出现FoxP 3表达细胞的从头群体。这些细胞表达高水平的CTLA-4，并且基于CTLA-4表达的细胞分选强烈富集具有抑制功能的表达FoxP 3+的细胞。在单独的IL-2中培养也产生具有抑制能力的细胞，其也与CTLA-4的出现相关。为了直接测试CTLA-4的作用，我们用CTLA-4转染了静息的人T细胞，发现这赋予了抑制作用，类似于天然Treg的抑制作用，即使这些细胞不表达FoxP 3。此外，FoxP 3的转染不诱导CTLA-4，并且这些细胞不具有抑制性。通过分离CTLA-4和FoxP 3的表达，我们的数据显示单独的FoxP 3表达不足以上调CTLA-4，然而，CD 4 + CD 25- T细胞的活化可以在能够抑制的T细胞亚群中诱导FoxP 3和CTLA-4。这些数据表明，活化的CD 4 + CD 25- T细胞获得抑制行为需要CTLA-4的表达，这是一种似乎由FoxP 3的表达促进但不依赖于FoxP 3的表达的特征。
The role of CTLA-4 in Regulatory T cell (Treg) function is not well understood. We have examined the role of CTLA-4 and its relationship with the transcription factor FoxP3 using a model of Treg induction in human peripheral blood. Activation of human CD4+CD25- T cells resulted in the appearance of a de novo population of FoxP3-expressing cells within 48h. These cells expressed high levels of CTLA-4 and cell sorting on expression of CTLA-4 strongly enriched for FoxP3+ expressing cells with suppressive function. Culture in IL-2 alone also generated cells with suppressive capacity which also correlated with the appearance of CTLA-4. To directly test the role of CTLA-4, we transfected resting human T cells with CTLA-4, and found that this conferred suppression, similar to that of natural Treg, even though these did not express FoxP3. Furthermore, transfection of FoxP3 did not induce CTLA-4 and these cells were not suppressive. By separating the expression of CTLA-4 and FoxP3, our data show that FoxP3 expression alone is insufficient to upregulate CTLA-4, however, activation of CD4+ CD25- T cells can induce both FoxP3 and CTLA-4 in a sub-population of T cells which are capable of suppression. These data suggest that the acquisition of suppressive behaviour by activated CD4+ CD25- T cells requires the expression of CTLA-4, a feature which is appears to be facilitated by, but is not dependent on, expression of FoxP3.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
64.8
作者：
Wan, Yisong Y.;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
DOI：
10.1073/pnas.0501701102
发表时间：
2005-04-05
影响因子：
11.1
作者：
Wan, YSY;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
5.4
作者：
Tang, QZ;Boden, EK;Bluestone, JA
通讯作者：
Bluestone, JA
影响因子：
32.4
作者：
TIVOL, EA;BORRIELLO, F;SHARPE, AH
通讯作者：
SHARPE, AH