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 lifelong infection elicits a marked host response, including a robust gastric IgA response. However, natural infection fails to yield protective immunity. Rather than providing protection, the chronic inflammatory response associated with natural infection can contribute to tissue damage and the pathogenesis of gastroduodenal disease, including atrophic gastritis, peptic ulcer, and gastric cancer. These immune responses are attributed to a subset of 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 modify the host response in a manner that prevents immune-mediated disease. Using animal models as a tool to understand the immunobiology of Helicobacter infections, several investigators have shown that effective vaccines can be developed. Thus, prophylactic and even therapeutic vaccines have been described in various animal models. The basis for the effectiveness of these vaccines appears related to their ability to alter the gastric immune response, from a homogeneous Th1 response to a mixed Th1 and Th2 response. Interestingly, immunity can occur in the absence of B cells, suggesting that novel IgA-independent mechanisms exist that confer protection against a luminal infection. Thus, H. pylori infection provides a model with which new mechanisms of immunological protection can be identified and applied to other mucosal infections.