Functional analysis of effector and regulatory T cells in a parasitic nematode infection
Functional analysis of effector and regulatory T cells in a parasitic nematode infection
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DOI：
10.1128/iai.01233-07
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发表时间：
2008-05-01
影响因子：
3.1
通讯作者：
Hartmann, Susanne
中科院分区：
文献类型：
--
作者：
Rausch, Sebastian;Huehn, Jochen;Hartmann, Susanne
寄生线虫通常调节T细胞反应性，主要在感染的慢性期。我们分析了CD 4阳性（CD 4（+））T效应（T-eff）细胞和调节性T（T-reg）细胞的作用，这些细胞来源于肠道线虫Heligmosomoides polygyrus慢性感染的小鼠。将不同的CD 4（+）T细胞亚群转移到随后感染H.多脑回常规T-eff细胞的连续转移赋予了保护作用，并导致H.多脑回感染的受体大约0.2%的CD 4（+）T细胞是H。基于CD 154表达的多脑回特异性，并且产生白细胞介素4（IL-4）和IL-13的细胞在CD 154（+）群体中高度富集。相比之下，过继转移的T-reg细胞，其特征在于标志物CD 25和CD 103和转录因子Foxp 3，对受者的蠕虫负担没有影响。进一步的分析表明，感染后不久，Foxp 3（+）T-reg细胞的数量在发炎组织中暂时增加，而效应/记忆样CD 103（+）Foxp（+）T-reg细胞在引流淋巴结和脾脏中全身性增加。此外，T-reg细胞代表了IL-10的潜在来源，并降低了IL-4的表达。最后，在体外条件下，来自感染小鼠的T-reg细胞比来自未感染小鼠的细胞是更有效的抑制剂。总之，我们的数据表明，少量的T-eff细胞具有促进宿主保护性免疫应答的能力，即使在T-reg细胞存在的情况下。
Parasitic nematodes typically modulate T-cell reactivity, primarily during the chronic phase of infection. We analyzed the role of CD4-positive (CD4(+)) T effector (T-eff) cells and regulatory T (T-reg) cells derived from mice chronically infected with the intestinal nematode Heligmosomoides polygyrus. Different CD4(+) T-cell subsets were transferred into naive recipients that were subsequently infected with H. polygyrus. Adoptive transfer of conventional T-eff 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 T-reg 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(+) T-reg cells temporarily increased in the inflamed tissue while effector/memory-like CD103(+) Foxp(+) T-reg cells systemically increased in the draining lymph nodes and spleen. In addition, T-reg cells represented a potential source of IL-10 and reduced the expression of IL-4. Finally, under in vitro conditions, T-reg cells from infected mice were more potent suppressors than cells derived from naive mice. In conclusion, our data indicate that small numbers of T-eff cells have the ability to promote host protective immune responses, even in the presence of T-reg cells.