Toll-like receptor ligands directly promote activated CD4+ T cell survival
Toll-like receptor ligands directly promote activated CD4+ T cell survival
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DOI：
10.4049/jimmunol.172.10.6065
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发表时间：
2004-05-15
影响因子：
4.4
通讯作者：
Turka, LA
中科院分区：
文献类型：
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作者：
Gelman, AE;Zhang, JD;Turka, LA
toll样受体（TLR）参与病原体相关分子模式（PAMPs）是优化细胞免疫应答的重要机制。APC TLR参与通过促进共刺激分子的上调和促炎细胞因子的分泌，间接增强活化的CD4(+) T细胞的增殖、分化和存活。然而，tlr也在CD4(+) T细胞上表达，这表明PAMPs也可能直接作用于活化的CD4(+) T细胞，介导功能反应。在这项研究中，我们发现激活的小鼠CD4(+) T细胞表达TLR-3和TLR-9，但不表达TLR-2和TLR-4。用dsRNA合成的TLR-3和TLR-9配体类似物poly（I:C）和CpG oligodeoxynucleotides （CpG DNA）处理高度纯化的活化CD4(+) T细胞，直接提高了它们的存活率，而不增加增殖。而TLR-2和TLR-4各自的配体肽聚糖和LPS则没有作用。通过poly（I:C）或CpG DNA介导的生存增强需要NF-kappaB激活，并与Bcl-x(L)上调相关。然而，只有CpG DNA，而没有poly（I:C）介导的作用。激活的CD4(+) T细胞需要TLR/IL-1R结构域包含适配分子髓样分化因子88。综上所述，我们的研究结果表明PAMPs可以直接促进活化的CD4(+) T细胞的存活，这表明T细胞上的tlr可以直接调节适应性免疫反应。
Toll-like receptor (TLR) engagement by pathogen-associated molecular patterns (PAMPs) is an important mechanism for optimal cellular immune responses. APC TLR engagement indirectly enhances activated CD4(+) T cell proliferation, differentiation, and survival by promoting the up-regulation of costimulatory molecules and the secretion of proinflammatory cytokines. However, TLRs are also expressed on CD4(+) T cells, suggesting that PAMPs may also act directly on activated CD4(+) T cells to mediate functional responses. In this study, we show that activated mouse CD4(+) T cells express TLR-3 and TLR-9 but not TLR-2 and TLR-4. Treatment of highly purified activated CD4(+) T cells with the dsRNA synthetic analog poly(I:C) and CpG oligodeoxynucleotides (CpG DNA), respective ligands for TLR-3 and TLR-9, directly enhanced their survival without augmenting proliferation. In contrast, peptidoglycan and LPS, respective ligands for TLR-2 and TLR-4 had no effect. Enhanced survival mediated by either poly(I:C) or CpG DNA required NF-kappaB activation and was associated with Bcl-x(L), up-regulation. However, only CpG DNA, but not poly(I:C)-mediated effects. on activated CD4(+) T cells required the TLR/IL-1R domain containing adaptor molecule myeloid differentiation factor 88. Collectively, our results demonstrate that PAMPs can directly promote activated CD4(+) T cell survival, suggesting that TLRs on T cells can directly modulate adaptive immune responses.