Di Tommaso A, Xiang Z, Bugnoli M, Pileri P, Figura N, Bayeli P F, Rappuoli R, Abrignani S, De Magistris M T
Immunobiology Research Institute Siena, University of Siena, Italy.
Infect Immun. 1995 Mar;63(3):1102-6. doi: 10.1128/iai.63.3.1102-1106.1995.
Colonization of human gastric mucosa with cytotoxic strains of the bacterium Helicobacter pylori is associated with peptic ulcer and with chronic gastritis. Since little is known about the T-cell response to H. pylori, we investigated the CD4+ T-cell response both in peripheral blood mononuclear cells (PBMCs) and at the site of infection. First, we compared the bulk PBMC proliferative response to the bacterium in individuals with and without symptoms of gastroduodenal disease. We found that the PBMCs from virtually all individuals proliferate in response to heat-inactivated bacteria. Second, we cloned H. pylori-specific CD4+ T lymphocytes from the PBMCs of three patients and from both the gastric mucosa and PBMCs of a fourth patient. We have found that CD4+ T-cell clones specific for H. pylori from peripheral blood samples and gastric mucosae of infected patients are major histocompatibility complex class II restricted and discriminate between several cytotoxic and noncytotoxic bacterial strains. Moreover, they are polyclonal in terms of T-cell receptor usage and major histocompatibility complex restriction. Our results demonstrate that the T-cell response to the whole bacterium in PBMCs does not correlate with antibody response, infection, or disease. However, H. pylori-specific CD4+ T cells are detectable, at the clonal level, in both the periphery and gastric mucosa of infected patients. Localization of these cells at the site of disease suggests they are effectors of the immune response to the bacteria.
细胞毒性幽门螺杆菌菌株在人胃黏膜的定植与消化性溃疡及慢性胃炎相关。由于对幽门螺杆菌的T细胞应答了解甚少，我们对外周血单核细胞（PBMC）和感染部位的CD4⁺T细胞应答进行了研究。首先，我们比较了患有和未患有胃十二指肠疾病症状个体的PBMC对该细菌的总体增殖反应。我们发现，几乎所有个体的PBMC都会对热灭活细菌产生增殖反应。其次，我们从三名患者的PBMC以及第四名患者的胃黏膜和PBMC中克隆了幽门螺杆菌特异性CD4⁺T淋巴细胞。我们发现，来自感染患者外周血样本和胃黏膜的幽门螺杆菌特异性CD4⁺T细胞克隆受主要组织相容性复合体II类限制，并能区分几种细胞毒性和非细胞毒性细菌菌株。此外，就T细胞受体的使用和主要组织相容性复合体限制而言，它们是多克隆的。我们的结果表明，PBMC中对整个细菌的T细胞应答与抗体应答、感染或疾病无关。然而，在感染患者的外周和胃黏膜中，均可在克隆水平检测到幽门螺杆菌特异性CD4⁺T细胞。这些细胞在疾病部位的定位表明它们是针对该细菌的免疫应答效应细胞。
