Novel mechanism of rapamycin in GVHD: increase in interstitial regulatory T cells.
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.
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- T-Lymphocytes, Regulatory
- Skin
- Sirolimus
- Mice, Inbred BALB C
- Mice
- Liver
- Intestines
- Immunology
- Graft vs Host Disease
- Forkhead Transcription Factors
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- T-Lymphocytes, Regulatory
- Skin
- Sirolimus
- Mice, Inbred BALB C
- Mice
- Liver
- Intestines
- Immunology
- Graft vs Host Disease
- Forkhead Transcription Factors