Helper T cell subsets for immunoglobulin A responses: oral immunization with tetanus toxoid and cholera toxin as adjuvant selectively induces Th2 cells in mucosa associated tissues.
Helper T cell subsets for immunoglobulin A responses: oral immunization with tetanus toxoid and cholera toxin as adjuvant selectively induces Th2 cells in mucosa associated tissues.
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DOI：
10.1084/jem.178.4.1309
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发表时间：
1993-10-01
影响因子：
15.3
通讯作者：
McGhee, J R
中科院分区：
文献类型：
--
作者：
Xu-Amano, J;Kiyono, H;Jackson, R J;Staats, H F;Fujihashi, K;Burrows, P D;Elson, C O;Pillai, S;McGhee, J R
抗原特异性B细胞对粘膜递送蛋白的应答依赖于CD 4阳性辅助性T（Th）细胞，口服免疫后Th 1和Th 2细胞应答的频率可决定粘膜抗体应答的水平和同种型。我们已经使用了基于蛋白质的疫苗，破伤风类毒素（TT），连同粘膜佐剂霍乱毒素（CT），用于小鼠的口服免疫，以研究在峰值抗体应答期间在胃肠道（GI）道的派伊尔集合淋巴结（PP）和脾脏（SP）中诱导的抗原特异性Th细胞亚群的性质。经口免疫TT和CT的小鼠在胃肠道中产生抗原特异性分泌型免疫球蛋白A（S-IgA）抗体，在血清中产生IgG和伊加抗体应答。将TT + CT口服免疫小鼠的PP和SP CD 4 + T细胞与抗原包被的乳胶微球一起培养，用于诱导增殖反应和计数产生细胞因子的CD 4 + T细胞。有趣的是，PP和SP CD 4 + T细胞培养物在免疫21天后显示IL-4和IL-5（Th 2型）产生的斑点形成细胞（SFC）的数量增加，而基本上没有注意到干扰素-γ（IFN-γ）或IL-2（Th 1型）SFC。细胞因子特异性北方印迹和RT-PCR还显示，从抗原刺激培养物中分离的CD 4 + T细胞中存在显著的IL-4和IL-5 mRNA水平，但不存在IFN-γ或IL-2 mRNA。然而，全身免疫TT和CT诱导抗原特异性IgG和IgM抗体，而不是伊加抗体在血清中。此外，IL-2和IFN-γ产生的Th 1型细胞，以及IL-4和IL-5分泌的Th 2型细胞中产生的SP。我们的研究结果表明，口服免疫TT和粘膜佐剂CT选择性诱导抗原特异性的Th 2型反应，这可能是主要的辅助细胞表型参与在胃肠道粘膜伊加反应。
Antigen-specific B cell responses to mucosally delivered proteins are dependent upon CD4-positive T helper (Th) cells, and the frequency of Th1 and Th2 cell responses after oral immunization may determine the level and isotype of mucosal antibody responses. We have used a protein- based vaccine, tetanus toxoid (TT), together with the mucosal adjuvant cholera toxin (CT), for oral immunization of mice to study the nature of antigen-specific Th cell subsets induced in Peyer's patches (PP) of the gastrointestinal (GI) tract and in the spleen (SP) during peak antibody responses. Mice orally immunized with TT and CT responded with antigen-specific secretory immunoglobulin A (S-IgA) antibodies in the GI tract, and with both IgG and IgA antibody responses in serum. PP and SP CD4+ T cells from mice orally immunized with TT plus CT were cultured with antigen-coated latex microspheres for induction of proliferative responses and for enumeration of cytokine producing CD4+ T cells. Interestingly, both PP and SP CD4+ T cell cultures showed increased numbers of IL-4- and IL-5 (Th2-type)-producing, spot-forming cells (SFCs) after 21 d of immunization, while essentially no interferon-gamma (IFN-gamma) or IL-2 (Th1-type) SFCs were noted. Cytokine-specific Northern blots and RT-PCR also revealed that significant IL-4 and IL-5 mRNA levels, but not IFN-gamma or IL-2 mRNA, were present in CD4+ T cells isolated from antigen-stimulated cultures. However, systemic immunization with TT and CT induced antigen-specific IgG and IgM but not IgA antibodies in serum. Further, both IL-2 and IFN- gamma-producing Th1-type cells as well as IL-4- and IL-5-secreting Th2- type cells were generated in SP. Our results show that oral immunization with TT and the mucosal adjuvant CT selectively induced antigen-specific Th2-type responses which may represent the major helper cell phenotype involved in mucosal IgA responses in the GI tract.