Novel mechanism of rapamycin in GVHD: increase in interstitial regulatory T cells.

Journal Article (Journal Article)

Rapamycin (RAPA) is an immunosuppressive drug that prevents and treats graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplant (HCT). One possible mechanism for its efficacy is induction of tolerance, through increased number or enhanced survival of regulatory T cells. In our experiments, B10.D2 BM and splenocytes were injected into lethally irradiated BALB/cJ recipients. The mice received i.p. injections of either RAPA or vehicle control on days 1-28. There was a significant survival advantage in RAPA-treated mice. Evaluation of the skin biopsies showed a dense cellular infiltrate in RAPA-treated mice. Further characterization of these cells revealed a higher percentage of regulatory T cells characterized by FoxP3-positive cells in high-dose RAPA-treated mice as compared with controls on day 30. This effect appears to be dose dependent. When peripheral blood analysis for FoxP3-positive cells was performed, there was no significant difference observed in the RAPA-treated mice as compared with control mice. These data show a novel mechanism of rapamycin in GVHD, accumulation of regulatory T cells in the GVHD target tissue: the skin.

Full Text

Duke Authors

Cited Authors

  • Palmer, JM; Chen, BJ; DeOliveira, D; Le, N-D; Chao, NJ

Published Date

  • February 2010

Published In

Volume / Issue

  • 45 / 2

Start / End Page

  • 379 - 384

PubMed ID

  • 19597415

Pubmed Central ID

  • PMC3649768

Electronic International Standard Serial Number (EISSN)

  • 1476-5365

Digital Object Identifier (DOI)

  • 10.1038/bmt.2009.140


  • eng

Conference Location

  • England