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.
OBJECTIVE
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.
Innere Medizin II, Medizinische Klinik, Universitätskliniken des Saarlandes, D-66421 Homburg/Saar, Germany. JC-Hoffmann@t-online.de
J C
JC
Hoffmann
K
K
Peters
S
S
Henschke
B
B
Herrmann
K
K
Pfister
J
J
Westermann
M
M
Zeitz
D000818:Animals; D000911:Antibodies, Monoclonal; D004136:Dinitrobenzenes; D005260:Female; D005434:Flow Cytometry; D007111:Immunity, Cellular; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000276:immunology* / Q000401:mortality; D008212:Lymphocyte Depletion / Q000009:adverse effects*; D009195:Peroxidase / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D012720:Severity of Illness Index; D013451:Sulfonic Acids; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000911:Antibodies, Monoclonal; D004136:Dinitrobenzenes; D013451:Sulfonic Acids; D009195:Peroxidase