Matysiak-Budnik Tamara, van Niel Guillaume, Mégraud Francis, Mayo Kathryn, Bevilacqua Claudia, Gaboriau-Routhiau Valérie, Moreau Marie-Christiane, Heyman Martine
INSERM EMI-0212, Faculté de Médecine Necker-Enfants Malades, Paris, France.
Infect Immun. 2003 Sep;71(9):5219-24. doi: 10.1128/IAI.71.9.5219-5224.2003.
The increase in the transcellular passage of intact antigens across the digestive epithelium infected with Helicobacter pylori may interfere with the regulation of mucosal immune responses. The aim of this work was to study the capacity of Helicobacter infection to inhibit the development of oral tolerance or to promote allergic sensitization and the capacity of a gastro-protective agent, rebamipide, to interfere with these processes in mice. Oral tolerance to ovalbumin (OVA) was studied in 48 C3H/He 4-week-old mice divided into four groups: (i) OVA-sensitized mice; (ii) OVA-"tolerized" mice (that is, mice that were rendered immunologically tolerant); (iii) H. felis-infected, OVA-tolerized mice; (iv) and H. felis-infected, OVA-tolerized, rebamipide-treated mice. Oral sensitization to hen egg lysozyme (HEL) was studied in 48 mice divided into four groups: (i) controls; (ii) HEL-sensitized mice; (iii) H. felis-infected, HEL-sensitized mice; and (iv) H. felis-infected, HEL-sensitized, rebamipide-treated mice. Specific anti-OVA or anti-HEL immunoglobulin E (IgE) and IgG1/IgG2a serum titers were measured by enzyme-linked immunosorbent assay. Additionally, the capacity of rebamipide to interfere with antigen presentation and T-cell activation in vitro, as well as absorption of rebamipide across the epithelial monolayer, was tested. H. felis infection led to the inhibition of oral tolerance to OVA, but rebamipide prevented this inhibitive effect of H. felis. H. felis infection did not enhance the sensitization to HEL, but rebamipide inhibited the development of this sensitization. Moreover, rebamipide inhibited in a dose-dependent manner antigen presentation and T-cell activation in vitro and was shown to be able to cross the epithelium at a concentration capable of inducing this inhibitory effect. We conclude that H. felis can inhibit the development of oral tolerance to OVA in mice and that this inhibition is prevented by rebamipide.
完整抗原经幽门螺杆菌感染的消化上皮细胞的跨细胞转运增加，可能会干扰黏膜免疫反应的调节。本研究旨在探讨幽门螺杆菌感染抑制口服耐受形成或促进过敏致敏的能力，以及胃保护剂瑞巴派特干扰小鼠上述过程的能力。在48只4周龄的C3H/He小鼠中研究了对卵清蛋白（OVA）的口服耐受，将其分为四组：（i）OVA致敏小鼠；（ii）OVA“耐受”小鼠（即产生免疫耐受的小鼠）；（iii）感染猫幽门螺杆菌的OVA耐受小鼠；（iv）感染猫幽门螺杆菌的OVA耐受且经瑞巴派特治疗的小鼠。在48只小鼠中研究了对鸡卵溶菌酶（HEL）的口服致敏，将其分为四组：（i）对照组；（ii）HEL致敏小鼠；（iii）感染猫幽门螺杆菌的HEL致敏小鼠；（iv）感染猫幽门螺杆菌的HEL致敏且经瑞巴派特治疗的小鼠。通过酶联免疫吸附测定法测量特异性抗OVA或抗HEL免疫球蛋白E（IgE）和IgG1/IgG2a血清滴度。此外，还测试了瑞巴派特在体外干扰抗原呈递和T细胞活化的能力，以及瑞巴派特跨上皮单层的吸收情况。猫幽门螺杆菌感染导致对OVA口服耐受的抑制，但瑞巴派特可预防猫幽门螺杆菌的这种抑制作用。猫幽门螺杆菌感染并未增强对HEL的致敏，但瑞巴派特抑制了这种致敏的发生。此外，瑞巴派特在体外以剂量依赖性方式抑制抗原呈递和T细胞活化，并且显示在能够诱导这种抑制作用的浓度下能够穿过上皮细胞。我们得出结论，猫幽门螺杆菌可抑制小鼠对OVA口服耐受的形成，而瑞巴派特可预防这种抑制作用。
