Northwestern Inflammatory Bowel Disease Center


	Our laboratory, headed by Dr. Barrett, is interested in the functional differentiation of intestinal T cells. We suspect that in inflammatory bowel diseases (IBD), that enteric (gut-derived) antigen is routed to the mesenteric lymph nodes where it activates peripheral T cells. The activation event determines the subsequent cell migration pattern by regulating the profile of surface homing receptors expressed. To address the factors that regulate the migration of intestinal T cells we have used an adoptive transfer model. Populations of antigen-specific, genetically-engineered transgenic (DO11.10) T cells are transferred into nontransgenic BALB/c mice. Cells are then activated in the periphery, which induces migration to the intestinal lamina propria. Our current studies show that the T helper type 1 (Th1) cytokine, IL-12 plays a critical role in directing intestinal T cell migration. These results have led to the investigation of the role of chemokines in intestinal T cell migration. The CXC family of chemokines specifically attracts Th1 cells.
	We suspect that the binding of chemokines (made in the intestine) regulates intestinal migration of of specific subsets of activated T cells. We plan to examine how activation of T cells in the periphery upregulate CXC receptor expression and how recognition of antigen in the tissue helps to accentuate inflammation by attracting greater numbers of activated Th1 T cells. These studies are relevant to IBD where tissue destruction is mediated by intense infiltrates of Th1-type T cells.