CD6 attenuates early and late signaling events, setting thresholds for T-cell activation.
CD6 attenuates early and late signaling events, setting thresholds for T-cell activation.
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DOI：
10.1002/eji.201040528
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发表时间：
2012-01
影响因子：
5.4
通讯作者：
Carmo, Alexandre M.
中科院分区：
文献类型：
--
作者：
Oliveira, Marta I.;Goncalves, Carine M.;Pinto, Mafalda;Fabre, Stephanie;Santos, Ana Mafalda;Lee, Simon F.;Castro, Monica A. A.;Nunes, Raquel J.;Barbosa, Rita R.;Parnes, Jane R.;Yu, Chao;Davis, Simon J.;Moreira, Alexandra;Bismuth, Georges;Carmo, Alexandre M.
T 谱系糖蛋白 CD6 通常被认为是 T 细胞激活的共刺激物。在这里，我们证明 CD6 显着降低超抗原刺激或 Abs 触发的 TCR 后的早期和晚期 T 细胞反应。通过测量单细胞响应超抗原的钙动员，我们发现表达大鼠 CD6 的人类 T 细胞的反应明显低于不表达外源受体的 T 细胞。当大鼠 CD6 的细胞质结构域被去除时，钙反应恢复，表明 CD6 的抑制特性可归因于其细胞质结构域。与 CD6 缺陷细胞或表达人 CD6 胞质缺失突变体的细胞相比，表达人 CD6 的 TCR 激活 Jurkat 细胞中的钙反应以及 T 细胞激活的晚期指标（如 IL-2 释放）也有所减弱。同样，在吗啉介导的 CD6 表达抑制后，人 T 淋巴细胞中由抗 CD3 触发的钙信号增强。最后，当用抗 CD166 抗体阻断 CD6-CD166 相互作用时，T 淋巴细胞的增殖增加，但当使用抗 CD6 抗体时，T 淋巴细胞的增殖受到抑制。我们的数据表明，CD6 是一种信号传导衰减剂，其单独表达（即在没有配体参与的情况下）足以抑制 T 细胞中的信号传导。
The T lineage glycoprotein CD6 is generally considered to be a costimulator of T-cell activation. Here, we demonstrate that CD6 significantly reduces early and late T-cell responses upon superantigen stimulation or TCR triggering by Abs. Measuring calcium mobilization in single cells responding to superantigen, we found that human T cells expressing rat CD6 react significantly less well compared with T cells not expressing the exogenous receptor. When the cytoplasmic domain of rat CD6 was removed, calcium responses were recovered, indicating that the inhibitory properties of CD6 are attributable to its cytoplasmic domain. Calcium responses, and also late indicators of T-cell activation such as IL-2 release, were also diminished in TCR-activated Jurkat cells expressing human CD6, compared with CD6-deficient cells or cells expressing a cytoplasmic deletion mutant of human CD6. Similarly, calcium signals triggered by anti-CD3 were enhanced in human T lymphocytes following morpholino-mediated suppression of CD6 expression. Finally, the proliferation of T lymphocytes was increased when the CD6–CD166 interaction was blocked with anti-CD166 Abs, but inhibited when anti-CD6 Abs were used. Our data suggest that CD6 is a signaling attenuator whose expression alone, i.e. in the absence of ligand engagement, is sufficient to restrain signaling in T cells.
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DOI：
10.1074/jbc.m111.230102
发表时间：
2011-09-02
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Bamberger M;Santos AM;Gonçalves CM;Oliveira MI;James JR;Moreira A;Lozano F;Davis SJ;Carmo AM
通讯作者：
Carmo AM
影响因子：
5.4
作者：
CARMO, AM;MASON, DW;BEYERS, AD
通讯作者：
BEYERS, AD
影响因子：
4.4
作者：
Castro, Monica A. A.;Oliveira, Marta I.;Carmo, Alexandre M.
通讯作者：
Carmo, Alexandre M.
影响因子：
15.9
作者：
IMBODEN, JB;JUNE, CH;LEDBETTER, JA
通讯作者：
LEDBETTER, JA
DOI：
10.1084/jem.181.6.2213
发表时间：
1995-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bowen MA;Patel DD;Li X;Modrell B;Malacko AR;Wang WC;Marquardt H;Neubauer M;Pesando JM;Francke U
通讯作者：
Francke U