Cellular immune responses are essential for the development of Helicobacter felis-associated gastric pathology

The bacteria Helicobacter pylori is a major human pathogen that infects ove r half of the world's population. Infection initiates a series of changes i n the gastric mucosa, beginning with atrophic gastritis and leading in some patients to peptic ulcer disease, mucosa-associated lymphomas, and gastric adenocarcinoma, Although this cascade of events clearly occurs, little is known about the role of the host immune response in disease progression, We have utilized the C57BL/6 Helicobacter felis mouse model to critically ana lyze the role of the adaptive immune response in the development of Helicob acter-associated gastric pathology. Infection of B and T cell deficient RAG -1(-/-) mice Or T cell-deficient TCR beta delta(-/-) mice with H, felis res ulted in high levels of colonization, but no detectable gastric pathology. Conversely, infection of B cell-deficient mu MT mice resulted in severe gas tric alterations identical with those seen in immunocompetent C57BL/6-infec ted mice, including gastric mucosal hyperplasia and intestinal metaplasia, These results demonstrate that the host T cell response is a critical media tor of Helicobacter-associated gastric pathology, and that B cells and thei r secreted Abs are not the effecters of the immune-mediated gastric patholo gy seen after H, felis infection. These results indicate that in addition t o specific Helicobacter virulence factors, the host immune response is an i mportant determinant of Helicobacter-associated disease.