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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
  1. J C Hoffmanna,
  2. K Petersa,
  3. S Henschkea,
  4. B Herrmanna,
  5. K Pfistera,
  6. J Westermannb,
  7. M Zeitza
  1. aInnere Medizin II, Medizinische Klinik, Universitätskliniken des Saarlandes, D-66421 Homburg/Saar, Germany, bZentrum Anatomie, Medizinische Hochschule Hannover, D-30623 Hannover, Germany
  1. Dr J C Hoffmann, Medizinische Klinik I, Universitätsklinikun Benjamin Franklin Hindenburgdamm 30, D12200 Berlin, Germany.JC-Hoffman{at}t-online.de

Abstract

BACKGROUND AND AIM Indirect evidence suggests that CD4+ T cells have a pathogenic while γδ 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, αβ Τ cells, or γδ T cells.

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

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

  • αβ T cells
  • γδ T cells
  • experimental colitis
  • inflammatory bowel disease
  • rat
  • Abbreviations used in this paper

    IBD
    inflammatory bowel disease
    ko
    knock out
    PALS
    periarteriolar lymphocyte sheath
    TCR
    T cell receptor
    TNBS
    2,4,6-trinitrobenzene sulphonic acid
    Th1
    T helper 1
    mAb
    monoclonal antibody
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  • Abbreviations used in this paper

    IBD
    inflammatory bowel disease
    ko
    knock out
    PALS
    periarteriolar lymphocyte sheath
    TCR
    T cell receptor
    TNBS
    2,4,6-trinitrobenzene sulphonic acid
    Th1
    T helper 1
    mAb
    monoclonal antibody
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