Abstract
We have previously shown that adoptively transferred CD4(+) T-cells mediate an chronic colitis in severe combined immune deficient (scid) mice. Colitis is accompanied by activation and apoptosis of Fas ligand and TNF-alpha expressing CD4(+) T-cells in the diseased colonic lamina propria (Eur. J. Immunol. 28:3655 (1998)). Here we investigate the apoptosis-inducing mechanism in these lamina propria infiltrating CD4(+) T-cells. We observe that freshly isolated lamina propria CD4(+) T-cells can kill Fas transfected P815 mastocytoma cells in a TCR/CD3 redirected chromium-release assay, but do not express TNF-alpha mediated cytotoxicity. Pre-incubation of the isolated lamina propria CD4(+) T-cells with an anti-FasL antiserum partially blocked killing of the Fas transfected target cells, indicating a role for the Fas-FasL system in the killing process. Treatment of scid mice with colitis with anti-FasL antiserum for 12 h blocked the apoptotic process in lamina propria CD4(+) T-cells by more than 65% compared to mice treated with control antiserum. Together, these results point towards the Fas-FasL and not the TNF-alpha-TNF-alpha receptor system as the primary apoptosis-inducing mechanism of lamina propria CD4(+) T-cells in this model of murine chronic colitis, and suggest an important role for the Fas-FasL system in the maintenance of homeostasis of locally proliferating T-cells.
| Original language | English |
|---|---|
| Journal | Immunology Letters |
| Volume | 78 |
| Issue number | 1 |
| Pages (from-to) | 7-12 |
| Number of pages | 6 |
| ISSN | 0165-2478 |
| Publication status | Published - 1 Aug 2001 |
Keywords
- Adoptive Transfer
- Animals
- Antigens, CD95
- Apoptosis
- Basement Membrane
- CD4-Positive T-Lymphocytes
- Colitis, Ulcerative
- Cytotoxicity, Immunologic
- Disease Models, Animal
- Fas Ligand Protein
- Immune Sera
- Intestinal Mucosa
- Membrane Glycoproteins
- Mice
- Mice, Inbred BALB C
- Mice, SCID