Absence of CD4+CD25+ regulatory T cells is associated with a loss of regulation leading to increased pathology in Helicobacter pylori‐infected mice
Absence of CD4+CD25+ regulatory T cells is associated with a loss of regulation leading to increased pathology in Helicobacter pylori‐infected mice
复制标题
CD4+CD25+调节性T细胞的缺失与调节性T细胞的丧失相关，从而导致幽门螺杆菌感染小鼠的病理学增加
DOI：
--
复制
发表时间：
2003
影响因子：
4.6
通讯作者：
E. Suri‐Payer
中科院分区：
文献类型：
--
作者：
S. Raghavan;M. Fredriksson;A. Svennerholm;J. Holmgren;E. Suri‐Payer
幽门螺杆菌在感染个体亚群中引起症状性慢性胃炎。机制(s)决定发展和严重程度的病理导致的症状尚不完全清楚。在幽门螺杆菌感染小鼠模型中，我们分析了免疫调节性CD4+CD25+ T细胞对幽门螺杆菌定植和胃炎的影响。胸腺C57BL/6 nu/nu小鼠分别用(a)淋巴结（LN）细胞重组(b)淋巴结细胞缺失CD25+ T细胞（CD25 - LN）或(c)完全不重组。小鼠经3 × 108H口腔感染。幽门螺杆菌SS1细菌。在接种后2周和6周，CD25 - LN细胞转染的胸腺小鼠的幽门螺杆菌定植量显著低于LN细胞转染的小鼠（P < 0.001）。接种后12周，定植量仍减少。与接受LN细胞的小鼠相比，移植CD25 - LN细胞的小鼠表现出更早的发病和更严重的胃炎。在体外实验中，接受CD25 - LN细胞的小鼠脾细胞在幽门螺杆菌抗原刺激下产生最高水平的IFN - γ，具有更高的幽门螺杆菌特异性DTH反应，并增加了胃粘膜中CD4+ T细胞和巨噬细胞的浸润。未转染T细胞的胸腺小鼠幽门螺杆菌定殖持续较高，胃上皮正常，无炎症细胞。总之，CD4+CD25+细胞减少幽门螺杆菌感染的免疫病理，可能是通过减少产生IFN‐γ的CD4+ T细胞的激活，即使是以胃粘膜中更高的幽门螺杆菌负荷为代价。
Helicobacter pylori induces symptomatic chronic gastritis in a subpopulation of infected individuals. The mechanism(s) determining the development and severity of pathology leading to symptoms are not fully understood. In a mouse model of H. pylori infection we analysed the influence of immunoregulatory CD4+CD25+ T cells on H. pylori colonization and gastritis. Athymic C57BL/6 nu/nu mice were reconstituted with (a) lymph node (LN) cells (b) LN cells depleted of CD25+ T cells (CD25– LN) or (c) not reconstituted at all. Mice were then infected orally with 3 × 108H. pylori SS1 bacteria. At 2 and 6 weeks after the inoculation there was a significant (P < 0·001) reduction in H. pylori colonization in athymic mice transferred with CD25– LN cells compared to mice transferred with LN cells. Colonization was still reduced at 12 weeks after inoculation. Mice transferred with CD25– LN cells showed an earlier onset and increased severity of gastritis as compared to mice receiving LN cells. Splenic cells isolated from mice receiving CD25– LN cells produced the highest level of IFN‐γ on stimulation with H. pylori antigens in vitro, had a higher H. pylori‐specific DTH response and increased infiltration of CD4+ T cells and macrophages in the gastric mucosa. Athymic mice not transferred with T cells had persistent high H. pylori colonization and displayed a normal gastric epithelium without inflammatory cells. In conclusion, CD4+CD25+ cells reduce immunopathology in H. pylori infection, possibly by reducing the activation of IFN‐γ producing CD4+ T cells, even at the expense of a higher H. pylori load in the gastric mucosa.
影响因子：
12.8
作者：
Suri-Payer, E;Cantor, H
通讯作者：
Cantor, H