Characterization of mucosal intranet formed by γδ/αβ T cells and epithelial cells

共同粘膜免疫系统（CMIS）已被证明是诱导（如肠道中的PP）和效应（如i-LP）组织之间的桥梁，是诱导抗原特异性IgA反应的关键因素。然而，我们最近的研究提供了新的证据，表明IgA抗体反应可以通过IgA的B细胞的B-1谱系以不依赖cmis的方式诱导。与cmis依赖的B-2细胞（IL-5R^+和IL-6R^+）不同，B-1细胞除了Th2型IL-5/IL-5R通路外，还受T细胞独立的细胞因子IL-15/IL-15R信号级联的调节。这些发现表明，粘膜免疫系统具有cmis依赖性（B-2）和非依赖性（B-1）两种诱导IgA应答的途径。对于大肠慢性炎症的诱导，我们发现免疫病理淋巴细胞是胸腺来源的th2型粘膜ββ T细胞（即IL-4产生细胞）的一个独特亚群。用TCRβ3和IL-4特异性单克隆抗体去除这些细胞，可抑制结肠炎的发展。关于肠道过敏，我们新的ova诱导模型提供了第一个直接证据，表明th2型细胞介导的肥大细胞、嗜酸性粒细胞和IgE浆细胞在结肠中的局部积聚与过敏症状的诱导有关。此外，研究表明，系统起源的抗原特异性th2型细胞优先归巢到大肠，用于stat6介导的IL-4和IL-13合成。尽管慢性炎症和过敏反应是两种完全不同的免疫疾病，但我们研究结果的一个有趣方面是，来自全身腔室的CD4^+ T细胞在远处粘膜腔室（如大肠）疾病状况的发展中发挥了关键作用。

The common mucosal immune system (CMIS) has been shown to be a key element which bridges between inductive (e.g. PP in the intestinal tract) and effector (e.g. i-LP) tissues for the induction of antigen-specific IgA response. However, our recent investigations provided new evidence that the IgA antibody response can be induced in an CMIS-independent manner via a B-1 lineage of IgA committed B cells. In contrast to the CMIS-dependent B-2 cells (IL-5R^+ and IL-6R^+), B-1 cells are under the regulation of a T cell independent cytokine IL-15/IL-15R signaling cascade in addition to the Th2 type IL-5/IL-5R pathway. These findings suggest that the mucosal immune system is equipped with both CMIS-dependent (B-2) and-independent (B-1) pathways for the induction of an IgA responses.For the induction of chronic inflammation in the large intestine, we showed that immunopathological lymphocytes were a unique subset of thymus derived mucosal ββ T cells of the Th2-type (i.e. IL-4 producer). Removal of these cells by treatment With mAbs specific for TCRβ3 and IL-4 resulted in the inhibition of colitis development. With regard to intestinal allergy, our new OVA-induced model provides the first direct evidence that a Th2-type cell mediated local accumulation of mast cells, eosinophils, and IgE plasma cells in colon is associated with the induction of allergic symptoms. Further, it was shown that systemically originating antigen-specific Th2-type cells preferentially homed to the large intestine for STAT6-mediated IL-4 and IL-13 synthesis. Although chronic inflammation and allergic reaction represent two totally different immunological diseases, an interesting aspect of our findings is that CD4^+ T cells originating from the systemic compartment played a key role in the development of a disease condition in a remote mucosal compartment such as the large intestine.