Pathogenesis of post-thymectomy autoimmune gastritis. Identification of anti-H/K adenosine triphosphatase-reactive T cells.
Pathogenesis of post-thymectomy autoimmune gastritis. Identification of anti-H/K adenosine triphosphatase-reactive T cells.
复制标题
胸腺切除术后自身免疫性胃炎的发病机制。
作者：
E. Suri‐Payer;P. Kehn;A. Cheever;E. Shevach
自体免疫性胃炎在3日龄BALB/c小鼠的胸腺切除术后自发发展（d3 Tx）。这些小鼠产生了胃壁细胞质子泵H/K ATP酶的自身抗体，新生胸腺中H/K ATP酶的异常表达阻止了胸腺切除术后疾病的诱导。为了表征介导自身免疫性胃炎的效应细胞，我们分离了富含H/K ATP酶的壁细胞微粒体制剂，并通过凝集素亲和层析进一步纯化了酶。这两种制剂诱导胃淋巴结细胞的显着增殖反应，这是由CD 4+，MHC II类限制性T细胞介导的。令人惊讶的是，对Ag有反应的T细胞只能在紧邻胃的淋巴结中被证明;当测试肠系膜或外周淋巴结时，很少或没有反应。很可能H/K ATP酶反应性T细胞实际上是这种疾病的效应细胞，因为它们只能在发生胃炎的小鼠中检测到，如抗壁细胞Ab、胃炎和存在能够将疾病转移到nu/nu小鼠中的细胞所示。H/K ATP酶特异性T细胞增殖反应可在胸腺切除后5周首次检测到，并在此时间点伴有高背景反应。这些后者的反应可能代表增强的同基因MLR，我们以前已经证明在d3 Tx小鼠中升高。H/K ATP酶反应性和自身反应性T细胞群的特征可能揭示破坏外周T细胞耐受性并导致器官特异性自身免疫性疾病发展的因素。
Autoimmune gastritis spontaneously develops following thymectomy of 3-day-old BALB/c mice (d3Tx). These mice develop autoantibodies to the gastric parietal cell proton pump, H/K ATPase, and aberrant expression of the H/K ATPase in the neonatal thymus prevents the induction of disease post-thymectomy. To characterize the effector cells mediating autoimmune gastritis, we isolated H/K ATPase-enriched preparations of parietal cell microsomes and further purified the enzyme by lectin affinity chromatography. Both preparations induced significant proliferative responses of gastric lymph node cells, which were mediated by CD4+, MHC class II-restricted T cells. Surprisingly, T cells reactive to the Ag could only be demonstrated in lymph nodes in the immediate proximity of the stomach; little or no response was seen when mesenteric or peripheral lymph nodes were tested. It is likely that the H/K ATPase-reactive T cells are actually the effector cells in this disease, as they could only be detected in mice that developed gastritis, as indicated by anti-parietal cell Ab, gastric inflammation, and the presence of cells capable of transferring disease into nu/nu mice. H/K ATPase-specific T cell proliferative responses could first be detected 5 wk post-thymectomy and were accompanied by high background responses at this time point. These latter responses may represent enhanced syngeneic MLRs, which we have previously shown to be elevated in d3Tx mice. Characterizations of the H/K ATPase-reactive and self-reactive T cell populations may reveal the factors that break peripheral T cell tolerance and lead to the development of organ-specific autoimmune disease.