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

• Published in: Gut Vol. 48; no. 4; pp. 489 - 495
• Main Authors: Hoffmann, J C, Peters, K, Henschke, S, Herrmann, B, Pfister, K, Westermann, J, Zeitz, M
• Format: Journal Article
• Language: English
• Published: England 01.04.2001
• Subjects: Animals; Antibodies, Monoclonal; Dinitrobenzenes; Female; Flow Cytometry; Immunity, Cellular; Inflammatory Bowel Diseases - chemically induced; Inflammatory Bowel Diseases - immunology; Inflammatory Bowel Diseases - mortality; Lymphocyte Depletion - adverse effects; Peroxidase - physiology; Rats; Rats, Inbred Lew; Severity of Illness Index; Sulfonic Acids; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Helper-Inducer - immunology
• ISSN: 0017-5749
• DOI: 10.1136/gut.48.4.489

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. 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. 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). 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.