Role of T lymphocytes in rat 2,4,6-trinitrobenzene sulphonic acid (TNBS) induced colitis: increased mortality after gamma delta T cell depletion and no effect of alpha beta T cell depletion

Background and aim-Indirect evidence suggests that CD4(+) T cells have a pa thogenic while gamma delta T cells have a protective role in the initiation and perpetuation of inflammatory bowel disease. To define the role of T ce ll subsets in a rat colitis model (2,4,6-trinitrobenzene sulphonic acid (TN BS)) we analysed colitis severity after effective depletion of T helper cel ls, alpha beta T cells, or gamma delta T cells. Methods-T helper cells, alpha beta T cells, or gamma delta T cells were dep leted using previously described monoclonal antibodies directed at the CD4 molecule (OX38), the CD2 molecule (OX34, both depleting CD4(+) T cells), th e ap T cell receptor (R73), and the gamma delta T cell receptor (V65). Depl etion was verified by flow cytometry and/or immunohistology. Colitis was in duced using intracolonic application of TNBS. Results-Surprisingly, depletion of T helper cells or alpha beta T cells had no influence on survival, macroscopic or microscopic scores, or myeloperox idase activity following colitis induction. In contrast, depletion of gamma delta T cells resulted in significantly increased mortality (V65: 73%, n=1 5) compared with controls (30%, n=13; p<0.03). In addition, colitis was his tologically more severe in the <gamma>delta T cell depleted group compared with controls (p<0.05). Conclusions-T helper cells or <alpha>beta T cells did not influence the ini tiation or perpetuation of rat TNBS colitis. In contrast, gamma delta T cel ls had a protective role in rat TNBS colitis as depletion caused increased mortality.