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Functional Analysis of Effector and Regulatory T Cells in a Parasitic Nematode Infection

机译:寄生线虫感染中效应和调节性T细胞的功能分析

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摘要

Parasitic nematodes typically modulate T-cell reactivity, primarily during the chronic phase of infection. We analyzed the role of CD4-positive (CD4+) T effector (Teff) cells and regulatory T (Treg) cells derived from mice chronically infected with the intestinal nematode Heligmosomoides polygyrus. Different CD4+ T-cell subsets were transferred into naïve recipients that were subsequently infected with H. polygyrus. Adoptive transfer of conventional Teff cells conferred protection and led to a significant decrease in the worm burdens of H. polygyrus-infected recipients. Roughly 0.2% of the CD4+ T cells were H. polygyrus specific based on expression of CD154, and cells producing interleukin 4 (IL-4) and IL-13 were highly enriched within the CD154+ population. In contrast, adoptive transfer of Treg cells, characterized by the markers CD25 and CD103 and the transcription factor Foxp3, had no effect on the worm burdens of recipients. Further analysis showed that soon after infection, the number of Foxp3+ Treg cells temporarily increased in the inflamed tissue while effector/memory-like CD103+ Foxp+ Treg cells systemically increased in the draining lymph nodes and spleen. In addition, Treg cells represented a potential source of IL-10 and reduced the expression of IL-4. Finally, under in vitro conditions, Treg cells from infected mice were more potent suppressors than cells derived from naïve mice. In conclusion, our data indicate that small numbers of Teff cells have the ability to promote host protective immune responses, even in the presence of Treg cells.
机译:寄生线虫通常在感染的慢性阶段通常调节T细胞反应性。我们分析了CD4阳性(CD4 + )T效应子(Teff)细胞和调节性T(Treg)细胞的作用,这些细胞源于长期感染肠线虫螺旋线虫的小鼠。将不同的CD4 + T细胞亚群转移到幼稚的受体中,随后再感染多螺旋体。常规Teff细胞的过继转移可提供保护,并导致感染多螺旋体的受体的蠕虫负担显着降低。根据CD154的表达,大约0.2%的CD4 + T细胞是H. polygyrus特异的,产生白介素4(IL-4)和IL-13的细胞在CD154 中高度富集+ 人口。相反,以标志物CD25和CD103以及转录因子Foxp3为特征的Treg细胞的过继转移对受体的蠕虫负担没有影响。进一步分析表明,感染后不久,发炎组织中Foxp3 + Treg细胞的数量暂时增加,而效应子/记忆样CD103 + Foxp + Treg细胞在引流淋巴结和脾脏中全身增加。另外,Treg细胞代表IL-10的潜在来源并降低IL-4的表达。最终,在体外条件下,来自感染小鼠的Treg细胞比来自纯稚小鼠的细胞更有效。总之,我们的数据表明,即使存在Treg细胞,少量Teff细胞也具有促进宿主保护性免疫反应的能力。

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