Expansion and activation of CD4(+)CD25(+) regulatory T cells in Heligmosomoides polygyrus infection.
Expansion and activation of CD4(+)CD25(+) regulatory T cells in Heligmosomoides polygyrus infection.
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DOI：
10.1002/eji.200636751
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发表时间：
2007-07
影响因子：
5.4
通讯作者：
Maizels, Rick M
中科院分区：
文献类型：
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作者：
Finney, Constance A M;Taylor, Matthew D;Wilson, Mark S;Maizels, Rick M
调节性T细胞对感染性生物体的应答不仅影响免疫和免疫病理学，而且影响对旁观者抗原的应答。感染胃肠道线虫寄生虫Heligmosomoides polygyrus的小鼠显示早期Th 2主导的免疫应答（第7-14天），但到第28天，强烈的调节特征是明显的，抗原特异性IL-10释放和携带表面TGF-β的CD 4 + T细胞的频率升高。来自感染小鼠的CD 4 + CD 25 + T细胞显示出增强的阻断体外效应T细胞增殖的能力。在感染过程中，CD 4 + CD 25+细胞数量急剧增加，CD 25 + Foxp 3+和CD 25 + Foxp 3-亚群平行生长。CTLA-4和糖皮质激素诱导的耐受相关受体，也与调节性T细胞功能相关，由于CD 25+细胞数量增加和CD 25-群体中表达增加而变得更加突出。CD 4 + T细胞表达CD 103的强度和频率均显著升高，其中在CD 25 + Foxp 3+细胞中扩增最大。虽然在CD 25 + Foxp 3+和CD 25 + Foxp 3-亚群中均观察到TGF-β表达，但后者在感染后显示出更高的TGF-β染色。这些数据表明，在慢性蠕虫感染中，Foxp 3+调节性T细胞受到刺激，特别是增加了CD 103表达，但其他群体发生了显著变化，包括CD 25 +TGF-β+ Foxp 3-细胞的扩增和CD 25-非调节性淋巴细胞上CTLA-4的诱导。
Regulatory T cell responses to infectious organisms influence not only immunity and immunopathology, but also responses to bystander antigens. Mice infected with the gastrointestinal nematode parasite Heligmosomoides polygyrus show an early Th2-dominated immune response (days 7–14), but by day 28 a strongly regulatory profile is evident with antigen-specific IL-10 release and elevated frequency of CD4+ T cells bearing surface TGF-β. CD4+CD25+ T cells from infected mice show enhanced capacity to block in vitro effector T cell proliferation. CD4+CD25+ cell numbers expand dramatically during infection, with parallel growth of both CD25+Foxp3+ and CD25+Foxp3– subsets. CTLA-4 and glucocorticoid-induced tolerance-associated receptor, also associated with regulatory T cell function, become more prominent, due to both expanded CD25+ cell numbers and increased expression among the CD25– population. Both intensity and frequency of CD103 expression by CD4+ T cells rise significantly, with greatest expansion among CD25+Foxp3+ cells. While TGF-β expression is observed among both CD25+Foxp3+ and CD25+Foxp3– subsets, it is the latter population which shows higher TGF-β staining following infection. These data demonstrate in a chronic helminth infection that Foxp3+ regulatory T cells are stimulated, increasing CD103 expression in particular, but that significant changes occur to other populations including expansion of CD25+TGF-β+Foxp3– cells, and induction of CTLA-4 on CD25– non-regulatory lymphocytes.