T-cell-mediated mucosal immunity in the absence of antibody: lessons from Helicobacter pylori infection

Approximately 50% of humanity is infected with Helicobacter pylori. This li felong infection elicits a marked host response, including a robust gastric IgA response. However, natural infection fails to yield protective immunit y. Rather than providing protection, the chronic inflammatory response asso ciated with natural infection can contribute to tissue damage and the patho genesis of gastroduodenal disease, including atrophic gastritis, peptic ulc er, and gastric cancer. These immune responses are attributed to a subset o f helper T cells, so-called Th1 cells, that enhance cell-mediated immunity and induce damage to the gastric epithelium. Thus, it is desirable to have effective vaccines that could prevent and cure infection and that may modif y the host response in a manner that prevents immune-mediated disease. Usin g animal models as a tool to understand the immunobiology of Helicobacter i nfections, several investigators have shown that effective vaccines can be developed. Thus, prophylactic and even therapeutic vaccines have been descr ibed in various animal models. The basis for the effectiveness of these vac cines appears related to their ability to alter the gastric immune response , from a homogeneous Th1 response to a mixed Th1 and Th2 response. Interest ingly, immunity can occur in the absence of B cells, suggesting that novel IgA-independent mechanisms exist that confer protection against a luminal i nfection. Thus, H pylori infection provides a model with which new, mechani sms of immunological protection can be identified and applied to other muco sal infections.