In vivo induction of type 1 and 2 immune responses against protein antigens
In vivo induction of type 1 and 2 immune responses against protein antigens
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DOI：
10.1093/intimm/9.4.523
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发表时间：
1997-04-01
影响因子：
4.4
通讯作者：
Thyphronitis, G
中科院分区：
文献类型：
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作者：
Comoy, EE;Capron, A;Thyphronitis, G
免疫反应对T(H)1或T(H)2的极化受几种尚不为人所知的机制的控制。本研究旨在探讨针对曼氏血吸虫寄生虫和细菌(破伤风梭菌)主要蛋白质抗原产生的免疫反应是否呈现出特征性的T-h谱。将曼氏杆菌28 kDa谷胱甘肽-S转移酶(Sm28-GST)或破伤风毒素C片段(TTC)与不同佐剂联合免疫小鼠，或以融合蛋白形式表达这些抗原的鼠伤寒沙门氏菌。研究抗原特异性免疫球蛋白G亚型、体内细胞因子mRNA的表达，以及体外抗原刺激后细胞因子的分泌。氢氧化铝中的任何一种蛋白免疫均可诱导T(H)2相关抗体(IgG1)和细胞因子(IL-4)应答。相反，表达TTC/Sm28-GST融合蛋白的重组鼠伤寒沙门氏菌诱导了T(H)1样反应，与产生针对这两种抗原的干扰素-γ和IgG2a抗体有关。当使用完全弗氏佐剂时，观察到非极化的轮廓，其特征是IL-4和干扰素-γ的表达以及强烈的特异性IgG1和IgG2a抗体反应。这些结果表明，某些蛋白质抗原对免疫反应的极化作用较弱，并且根据所使用的佐剂的不同，可以针对同一抗原诱导不同的细胞因子谱。
Polarization of the immune response towards T(h)1 or T(h)2 profiles is under the control of several, not yet well known, mechanisms. The present study was undertaken to investigate whether immune responses generated against major protein antigens, of parasitic (Schistosoma mansoni) and bacterial (Clostridium tetani) origin, present characteristic T-h profiles. Mice were immunized with a single dose of S. mansoni 28 kDa glutathione-S-transferase (Sm28-GST) or tetanus toxin fragment c (TTc) in combination with different adjuvants, or Salmonella typhimurium expressing these antigens as a fusion protein. Antigen-specific IgG isotypes and cytokine mRNA expression in vivo, as well as cytokine secretion after in vitro antigen stimulation were studied. Immunizations with either protein in aluminum hydroxide induced a strong T(h)2-associated antibody (IgG1) and cytokine (IL-4) response. In contrast, the recombinant S. typhimurium, expressing the TTc/Sm28-GST fusion protein, induced a T(h)1-like response, associated with the production of IFN gamma- and IgG2a antibodies against both antigens. When complete Freund's adjuvant was used, a non-polarized profile was observed, characterized by expression of both IL-4 and IFN-gamma as well as strong specific IgG1 and IgG2a antibody responses. These results indicated that some protein antigens play a weak role in polarizing the immune response and that contrasting cytokine profiles could be induced against the same antigen, depending on the adjuvant employed.