Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn's disease
| Autor: | T. Ten Hove, C. van Montfrans, Maikel P. Peppelenbosch, S. J. H. Van Deventer |
|---|---|
| Přispěvatelé: | Extramural researchers, Faculteit der Geneeskunde |
| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
Adult
musculoskeletal diseases CD3 Complex T-Lymphocytes CD3 Apoptosis Jurkat cells Jurkat Cells CD28 Antigens Crohn Disease Gastrointestinal Agents Intestinal mucosa Humans Medicine Intestinal Mucosa skin and connective tissue diseases Gastrointestinal agent biology business.industry Gastroenterology Antibodies Monoclonal CD28 T lymphocyte Infliximab stomatognathic diseases Treatment Outcome Immunology Commentary biology.protein sense organs business Biomarkers medicine.drug |
| Zdroj: | Gut, 50(2), 206-211. BMJ Publishing Group |
| ISSN: | 0017-5749 |
| Popis: | Background and aims: Treatment with infliximab induces remission in about 70% of patients with steroid refractory Crohn9s disease. Because Crohn9s disease is considered to be mediated by uncontrolled activation of mucosal T lymphocytes, we hypothesised that infliximab could induce apoptosis of T lymphocytes. Methods: Induction of apoptosis in vivo was studied in 10 patients with therapy refractory Crohn9s disease. In vitro, resting or stimulated Jurkat T cells were incubated with infliximab. Results: Infusion of infliximab (5 mg/kg) in steroid refractory patients with Crohn9s disease induced a clinical response in 9/10 patients but did not influence expression of activation markers, homing receptors, memory cells, Fas expression, or Bax/Bcl-2 expression on peripheral blood T lymphocytes. In contrast, a significant increase in CD3 and TUNEL positive cells within colonic biopsies was detected 24 hours after infusion of infliximab, suggesting that infliximab stimulates apoptosis of activated T lymphocytes but not of resting T cells. To test this hypothesis, the effects of infliximab on Jurkat T cells were investigated. We observed that infliximab induced apoptosis and an increase in the Bax/Bcl-2 ratio of CD3/CD28 stimulated Jurkat T cells but not of unstimulated Jurkat cells. Conclusions: Our data indicate that infliximab treatment causes a rapid and specific increase in apoptosis of T lymphocytes in the gut mucosa. These findings may explain the rapid and sustained therapeutic effects of infliximab in Crohn9s disease. |
| Databáze: | OpenAIRE |
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