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

Abstract

Background and aim: Indirect evidence suggests that CD4+ T cells have a pathogenic while gammadelta 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, alphabeta T cells, or gammadelta T cells.

Methods: T helper cells, alphabeta T cells, or gammadelta 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 alphabeta T cell receptor (R73), and the gammadelta 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 alphabeta T cells had no influence on survival, macroscopic or microscopic scores, or myeloperoxidase activity following colitis induction. In contrast, depletion of gammadelta 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 gammadelta T cell depleted group compared with controls (p<0.05).

Conclusions: T helper cells or alphabeta T cells did not influence the initiation or perpetuation of rat TNBS colitis. In contrast, gammadelta T cells had a protective role in rat TNBS colitis as depletion caused increased mortality.

Figure 1

No significant effect of αβ T cell depletion on colitis severity. Mean (95% confidence interval) values for (A) macroscopic score, (B) microscopic score, (C) myeloperoxidase (MPO) activity, and (D) survival (Kaplan-Meier analysis) comparing isotype matched control monoclonal antibody (mAb) (TS2/9, n=13) and the anti-αβ T cell receptor (TCR) mAb (R73, n=12). A dose of 200 µg followed by 100 µg of each mAb was started two days prior to colitis induction and continued on days −1, 0, 2, 4, 6, 8, and 10 after colitis induction.

Figure 2

Increased mortality of γδ T cell depleted rats with TNBS colitis. Mean (95% confidence interval) values for (A) macroscopic score, (B) microscopic score, (C) myeloperoxidase (MPO) activity, and (D) survival (Kaplan-Meier analysis) comparing isotype matched control monoclonal antibody (mAb) (TS2/9, n=13) and the anti-γδ T cell receptor (TCR) mAb (V65, n=15).