Toll-like receptor 2 signaling modulates the functions of CD4+CD25+ regulatory T cells
Toll-like receptor 2 signaling modulates the functions of CD4+CD25+ regulatory T cells
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DOI：
10.1073/pnas.0601554103
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发表时间：
2006-05-02
影响因子：
11.1
通讯作者：
Liew, FY
中科院分区：
文献类型：
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作者：
Liu, HY;Komai-Koma, M;Liew, FY
Toll样受体是天然免疫系统和获得性免疫系统的主要感受器，在对病原体结构保守成分的应答中起着关键作用。合成细菌脂蛋白(BLP)Pam3Cys-SK4是一种TLR2激动剂，能够调节T细胞免疫反应。我们在这里显示，BLP与抗CD3抗体[T细胞受体(TCR)激活]一起，在没有抗原提呈细胞的情况下，诱导了CD4(+)CD25(+)调节性T细胞(Tregs)和CD4(+)CD25(-)(效应)T细胞的增殖。扩张的Tregs显示出短暂的抑制活性丧失。此外，BLIP通过增加IL-2的分泌而使效应器对Tregs的抑制产生抵抗。在T细胞受体激活后8~15h，BLP还可短暂抑制Tregs中Foxp3(X连锁叉头/翼状螺旋转录因子)的表达。与此观察一致的是，BLP刺激的Tregs在严重联合免疫缺陷小鼠中恢复了抑制活性，并防止了效应器诱导的自发性结肠炎。我们的结果表明，在T细胞上表达的TLR可能直接调节免疫反应，这是一条以前未知的途径。因此，在急性细菌感染期间，BLIP可以通过扩展效应器和减弱Tregs的抑制活性来迅速提高宿主的适应性免疫。在这个过程中，BLP还扩大了Treg，当感染消退时，Treg恢复其抑制活动，以及时限制可能由过度激活的效应器导致的潜在自身免疫。
Toll-like receptors (TLRs) are primary sensors of both innate and adaptive immune systems and play a pivotal role in response against structurally conserved components of pathogens. Synthetic bacterial lipoprotein (BLP) Pam3Cys-SK4 is a TLR2 agonist that is capable of modulating T cell immune responses. We show here that BLP, together with anti-CD3 antibody [T cell receptor (TcR) activation], induced proliferation of both CD4(+)CD25(+) regulatory T cells (Tregs) and CD4(+)CD25(-) (effector) T cells in the absence of antigen-presenting cells. The expanded Tregs showed a transient loss of suppressive activity. Moreover, BLIP rendered effectors resistant to the suppression of Tregs by increasing IL-2 secretion. BLP also transiently suppressed the induction of Foxp3 (X-linked forkhead/winged helix transcription factor) mRNA in Tregs at the first 8-15 h after T cell receptor activation. Consistent with this observation, BLP-stimulated Tregs regained their inhibitory activity and prevented spontaneous colitis induced by effectors in severe combined immunodeficient mice. Our results demonstrate a previously unrecognized pathway by which TLR expressed on T cells may directly modulate the immune response. Thus, during an acute bacterial infection, BLIP may rapidly increase the host's adaptive immunity by expanding effectors and also by attenuating the suppressive activity of Tregs. In the process, BLP also expands the Tregs, which recover their suppressive activity when the infection has subsided, in time to limit potential auto-immunity that might result from the overactivated effectors.