Inhibition of human CD4+CD25+high regulatory T cell function
Inhibition of human CD4+CD25+high regulatory T cell function
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DOI：
10.4049/jimmunol.169.11.6210
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发表时间：
2002-12-01
影响因子：
4.4
通讯作者：
Hafler, DA
中科院分区：
文献类型：
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作者：
Baecher-Allan, C;Viglietta, V;Hafler, DA
CD4(+)CD25（+高）T细胞是自身反应性T细胞的有效调节因子。然而，目前尚不清楚调节性CD4(+)CD25（+高）细胞如何区分对微生物Ags的理想炎症免疫反应和自身反应性T细胞的潜在病理反应。在这项研究中，建立了一个体外模型，允许调节性CD4(+)CD25（+high）和应答性CD4(+) T细胞的差异激活。如果CD4(+)CD25（+高）调节性细胞被强烈激活，它们只维持了15小时的抑制效应功能，而较弱的TCR刺激产生的调节性细胞在激活后60小时仍具有抑制作用。相比之下，强烈激活的CD4（+）应答T细胞在所有时间点都对调节有抵抗力，而弱刺激的CD4（+）细胞在激活后38或60小时前对抑制敏感，这取决于刺激的强度。CD4(+)CD25（+高）细胞介导的抑制程度也取决于ag特异性系统中的刺激强度。因此，TCR信号越强，应答细胞对抑制的抵抗就越迅速、越彻底。
CD4(+)CD25(+high) T cells are potent regulators of autoreactive T cells. However, it is unclear how regulatory CD4(+)CD25(+high) cells discriminate between desirable inflammatory immune responses to microbial Ags and potentially pathologic responses by autoreactive T cells. In this study, an in vitro model was created that allowed differential activation of regulatory CD4(+)CD25(+high) and responder CD4(+) T cells. If CD4(+)CD25(+high) regulatory cells were strongly activated, they maintained suppressive effector function for only 15 h, while stimulation with weaker TCR stimuli produced regulatory cells that were suppressive until 60 h after activation. In contrast, strongly activated CD4(+) responder T cells were resistant to regulation at all time points, while weakly stimulated CD4(+) cells were sensitive to suppression until 38 or 60 h after activation depending upon the strength of the stimulus. The extent of suppression mediated by CD4(+)CD25(+high) cells also depended on the strength of stimulation in an Ag-specific system. Thus, the stronger the TCR signal, the more rapidly and more completely the responder cells become refractory to suppression.