CHANGES IN HUMAN MUCOSAL GAMMA-DELTA T-CELL REPERTOIRE AND FUNCTION-ASSOCIATED WITH THE DISEASE PROCESS IN INFLAMMATORY BOWEL-DISEASE

Background: Although gamma delta T cells are a major component of the human intestinal mucosa, it is not clear what role they play in mucosa l immunity or if they are involved in the disease process of inflammat ory bowel disease (IBD).Materials and Methods: Flow cytometry and reve rse transcriptase-polymerase chain reaction (RT-PCR) assays were used to identify quantitative and qualitative changes in the repertoire of gamma delta T cells present in surgical and/or biopsy samples of norma l and inflamed colon from individual patients with ulcerative colitis (UC) or Crohn's disease (CD). Cytokine production and the ability to a dhere to and interact with colonic fibroblasts were used to compare th e functional properties of gamma delta T cells isolated from the norma l and diseased colonic mucosa. Results: Increased numbers of gamma del ta T cells localized in areas of inflammation and tissue injury were f ound in the majority of patients, irrespective of the type of IBD pres ent. This expansion was attributable to an increase in V delta 1(+) ce lls expressing a V delta 1-(D delta 3)-J delta 1-encoded T cell recept or and was seen in patients with severe disease as well as those with newly diagnosed or less severe forms of IBD. Among T cells present in the inflamed mucosa of patients with CD, gamma delta T cells, particul arly V delta 1(+) cells, were a major source of the proinflammatory cy tokine interferon-gamma and could interact with colonic fibroblasts. C onclusions: Our results demonstrate that the chronic inflammatory immu ne response characteristic of IBD is associated with distinct changes in the number, distribution, composition, and function of mucosal gamm a delta T cells. Through the production of cytokines and physical inte raction with other cells, gamma delta T cells can perform an immunoreg ulatory function and contribute to the pathophysiology of IBDs.