Fujihashi K, McGhee J R, Yamamoto M, Hiroi T, Kiyono H
Department of Oral Biology, University of Alabama at Birmingham, 35294, USA.
Ann N Y Acad Sci. 1996 Feb 13;778:55-63. doi: 10.1111/j.1749-6632.1996.tb21114.x.
In this short review, we first described experiments that show that prolonged oral immunization with a protein vaccine, such as DT, induced systemic unresponsiveness in the presence of antigen-specific mucosal IgA responses. Mucosal T cells, such as IEL, may play an important role for the maintenance of antigen-specific IgA responses because these T cells are able to respond to stimulation signals provided by antigen even when T-cell unresponsiveness was induced in systemic tissue, such as spleen of mice orally tolerized with the protein DT. Inasmuch as IEL contain a high frequency of gamma delta T cells, it was logical to postulate that mucosal gamma delta T cells are essential regulatory T cells for the induction of IgA responses in oral tolerance. To this end, our previous studies showed that adoptive transfer of mucosal gamma delta T cells from IEL of mice orally tolerized with SRBC to the recipient mice with systemic unresponsiveness to the same antigen resulted in the abrogation of unresponsiveness to Ig synthesis, including those of IgA isotype. In this regard, when the mucosal immune system of TCR-delta-/- and their control mice was examined, lower numbers of IgA antibody-producing cells were noted in TCR-delta-/- mice in comparison to control background mice. Further, the level of IgA in fecal extracts was also low in TCR-delta-/- mice. These findings suggested that loss of gamma delta T cells in down-regulation of IgA B-cell responses.
在这篇简短的综述中，我们首先描述了一些实验，这些实验表明，用蛋白质疫苗（如白喉破伤风联合疫苗）进行长时间口服免疫，在存在抗原特异性黏膜IgA反应的情况下会诱导全身无反应性。黏膜T细胞，如肠上皮内淋巴细胞（IEL），可能在维持抗原特异性IgA反应中起重要作用，因为即使在全身组织（如用蛋白质白喉破伤风联合疫苗口服耐受的小鼠脾脏）中诱导了T细胞无反应性，这些T细胞仍能够对抗原提供的刺激信号作出反应。鉴于IEL中含有高频的γδ T细胞，合乎逻辑的推测是，黏膜γδ T细胞是口服耐受中诱导IgA反应的关键调节性T细胞。为此，我们之前的研究表明，将经绵羊红细胞口服耐受的小鼠IEL中的黏膜γδ T细胞过继转移到对相同抗原具有全身无反应性的受体小鼠中，会导致对Ig合成（包括IgA同种型）的无反应性被消除。在这方面，当检查TCR-δ-/-小鼠及其对照小鼠的黏膜免疫系统时，与对照背景小鼠相比，TCR-δ-/-小鼠中产生IgA抗体的细胞数量较少。此外，TCR-δ-/-小鼠粪便提取物中的IgA水平也较低。这些发现表明γδ T细胞的缺失会下调IgA B细胞反应。
