| The mucosal immune system is the first line of defense against many invading pathogens. A vast number of lymphocytes are present to protect the host. Many of these lymphocytes are classically derived. However, a portion of these lymphocytes, for example components of the intraepithelial lymphocyte compartment (IEL), appear phenotypically distinct from classical lymphocytes. A significant number of T lymphocytes in the IEL compartment express TCRγδ chains. A fraction of the T lymphocytes in the IELs appear to develop extrathymically, possibly arising from the recently described “cryptopatches”. While requirements for thymic T lymphocyte maturation have been extensively studied, the maturation of extrathymic T lymphocytes remains largely uncharacterized. To address this issue, the development of intestinal IELs was investigated in mice deficient for the protein tyrosine phosphatase CD45.; The gastric Helicobacter species are a group of pathogens that the mucosal immune system must control. H. pylori infection in humans results in gastritis. H. pylori diseases can progress to gastric ulcer as well as gastric cancer formation. Many animal models have been developed to study H. pylori infection. However, H. pylori can not colonize mice well, making investigations into the immune response to H. pylori difficult. An alternative mouse model of Helicobacter infection has been developed, utilizing H. felis. In the C57BL/6-H. felis mouse model, severe gastritis and gastric epithelial pathology develops, similar to human infection with H. pylori. To investigate the role of lymphocytes in the development of gastric epithelial pathology, mice deficient for B and T lymphocytes (Rag-1−/−), T lymphocytes (TCRβδ −/−) or B lymphocytes (μMT) were infected with H. felis. The mice lacking T lymphocytes did not develop gastric pathology after infection, demonstrating their role in pathology initiation. To aid future investigations into mechanisms of pathology development and antigen specificity issues, an adoptive transfer system was developed utilizing Rag-1−/− mice as recipients. This system has demonstrated that CD4+ T lymphocytes are sufficient to induce epithelial pathology after H. felis infection. These investigations will allow better understanding of the Helicobacter induced diseases, and potentially lead to safe and effective methods to control H. pylori infection in humans. |
