Analysis of Cytokines in the Early Development of Gastric Secondary Lymphoid Follicles inHelicobacter pylori-Infected BALB/c Mice with Neonatal Thymectomy

Abstract

Immunological interaction between the host and Helicobacter pylori seems to play a critical role in follicular formation in gastric mucosa. We reported H. pylori-induced follicular gastritis model using neonatally thymectomized mice. In this study, we investigated the involvement of various cytokines in this model. BALB/c mice were thymectomized on the third day after birth (nTx). At 6 weeks old, these mice were orally infected with H. pylori. Histological studies showed that follicular formation occurred from 8 weeks after the infection and that most of the infiltrating lymphocytes were CD4؉ and B cells. Neutrophils increased transiently at 1 week after the infection. Gamma interferon, interleukin-7 (IL-7), and IL-7 receptor were expressed in the stomach of the nTx mice irrespective of the infection. In contrast, expressions of the tumor necrosis factor alpha, IL-4 and lymphotoxin-␣ genes were remarkably upregulated by the infection. Our findings suggest that follicular formation may require cooperative involvement of a Th2-type immune response, tumor necrosis factor alpha and lymphotoxin-␣ in addition to the Th1-type immune response in H. pylori-induced gastritis in nTx mice.

Immunogenetic analysis of gastric MALT lymphoma-like lesions induced by Helicobacter pylori infection in neonatally thymectomized mice

“…In previous studies, we succeeded in inducing lymphoid follicle formation in association with chronic gastritis by H. pylori infection in BALB/c mice that were thymectomized on the 3rd day after birth. 5,12 In the present study, we extended our previous findings and established a model of gastric MALT lymphoma-like lesions after long-term infection with H. pylori using the same animals.…”

“…Supporting this idea, we observed, in addition to IFN-g, expression of IL-4, a representative Th2-type cytokine, in the gastric mucosa of only H. pylori-infected BALB/c mice with nTx that developed lymphoid follicles. 5,12 Taken together, our previous and present findings suggest that genetic background and the resulting specific immune responses to H. pylori have critical roles in the development of MALT lymphoma-like lesions.…”

“…At 1 month (10 weeks of age) after infection, Table 1 however, clusters of mononuclear cells appeared at the bottom of the lamina propria in the gastric mucosa as reported previously. 5 There was a distinct change in lymphoid cell infiltration 2 months after infection (14 weeks of age, Figure 1b); unlike noninfected nTx mice, infected mice had lymphoid follicle development in the corpus mucosa. Follicle formation and infiltration of intraepithelial lymphocytes were enhanced in a time-dependent manner (follicles; 60% (6/10) at 2 months, 40% (4/10) at 4 months, 80% (8/10) at 6 months and 90% (9/10) at 12 months; Figure 1b-d), whereas no follicles formed in noninfected nTx mice throughout the experiment (Figure 1a).…”

“…[8][9][10][11] In previous studies, we demonstrated that infection of BALB/c nTx mice with mouse-adapted H. pylori permitted successful colonization of H. pylori in the corpus, leading to the formation of follicular gastritis 2 months after infection in association with appearance of a Th2-type reaction. 5,12 In the present study, therefore, we extended our previous findings and attempted to develop gastric MALT lymphomalike lesions in nTx mice with long-term H. pylori infection, and performed immunogenetic analyses.…”

“…[1][2][3][4] Immunologic interactions between the host and H. pylori seem to have critical roles in the development of follicular gastritis, which appears to be an important condition preceding gastric MALT lymphoma. 5 Recently, an API2-MALT1 fusion transcript derived from t(11;18) was reported to be involved in the pathogenesis of H. pylori-uninfected gastric MALT lymphoma. 6,7 On the other hand, the pathogenesis of H. pylori-positive gastric MALT lymphoma without t(11;18) remains unclear.…”