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

Background and aim-Indirect evidence suggests that CD4(+) T cells have a pathogenic while gamma delta T cells have a protective role in the initiation and perpetuation of inflammatory bowel disease. To define the role of T cell subsets in a rat colitis model (2,4,6-trinitrobenzene sulphonic acid (TNBS)) we analysed colitis severity after effective depletion of T helper cells, alpha beta T cells, or gamma delta T cells. Methods-T helper cells, alpha beta T cells, or gamma delta T cells were depleted using previously described monoclonal antibodies directed at the CD4 molecule (OX38), the CD2 molecule (OX34, both depleting CD4(+) T cells), the ap T cell receptor (R73), and the gamma delta T cell receptor (V65). Depletion was verified by flow cytometry and/or immunohistology. Colitis was induced 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 myeloperoxidase activity following colitis induction. In contrast, depletion of gamma delta T cells resulted in significantly increased mortality (V65: 73%, n=15) compared with controls (30%, n=13; p<0.03). In addition, colitis was histologically 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 initiation or perpetuation of rat TNBS colitis. In contrast, gamma delta T cells had a protective role in rat TNBS colitis as depletion caused increased mortality.