Effects of different immunosuppressive regimens on regulatory T-cells in noninflamed colon of liver transplant recipients

✍ Scribed by R.C. Verdonk; E.B. Haagsma; M.R. Jonker; L.I.H. Bok; J.H. Zandvoort; J.H. Kleibeuker; K.N. Faber; G. Dijkstra

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 239 KB
• Volume: 13
• Category: Article
• ISSN: 1078-0998
• DOI: 10.1002/ibd.20087

✦ Synopsis

Background:

Regulatory T-cells (Treg) are natural suppressors of autoimmunity. Previous studies indicate that immunosuppressive drugs, especially calcineurin-inhibitors, may interfere with Treg homeostasis. Inflammatory bowel disease (IBD) can relapse or develop de novo after liver transplantation. IBD is associated with a relative deficiency of Treg. The aim of this study was to determine the effect of long-term immunosuppression on the presence of Treg in the noninflamed colonic mucosa of liver transplant recipients.

Methods: Colonic biopsies of normal mucosa of 36 liver transplant recipients on different types of immunosuppression and 11 controls were studied. Treg marker Foxp3 and Treg products transforming growth factor-␤ (TGF-␤) and interleukin-10 (IL-10) were studied by quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry. TGF-␤-induced Smad-protein 3 and 7 were studied by Q-PCR.

Results: No significant differences between controls and patients were observed in IL-10, TGF-␤, and Smad expression. Mucosal Foxp3 mRNA levels and Foxp3ϩCD3ϩ cells were significantly reduced in transplant recipients using prednisone/azathioprine/tacrolimus compared with controls but no direct relationship between Foxp3 expression and 1 specific drug was detected.

Conclusions:

These results challenge the hypothesis that calcineurin-induced reduction of Treg or TGF-␤ expression predisposes nontransplanted tissue to inflammation, but indicate that combined immunosuppression hampers Treg development in the intestine.