Terrence Barrett, MD
Professor, Medicine-Gastroenterology and Hepatology,
Microbiology-Immunology and Surgery-Organ Transplantation
Feinberg School of Medicine
The laboratory of Dr. Terrence Barrett is interested in the functional differentiation of intestinal T cells. They 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, Dr. Barrett’s laboratory has used an adoptive transfer model. Populations of antigen-specific 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. Dr. Barrett’s lab suspects that the binding of chemokines (made in the intestine) regulates intestinal migration of specific subsets of activated T cells. They 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.