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Prevention of graft-versus-host disease by a novel immunosuppressant, PG490-88, through inhibition of alloreactive T cell expansion.

Publication ,  Journal Article
Chen, BJ; Liu, C; Cui, X; Fidler, JM; Chao, NJ
Published in: Transplantation
November 27, 2000

BACKGROUND: PG490-88 is a water soluble, semisynthetic derivative of a novel compound PG490 (triptolide) purified from the Chinese herb Tripterygium Wilfordii Hook F. METHODS: PG490-88 was administrated into recipient mice in a model (B10.D2-->BALB/c) of lethal graft-versus-host disease (GVHD) to study the effects of PG490-88 on GVHD and on the various steps involved in the pathological course of GVHD. RESULTS: Injection of PG490-88 i.p. at a dose of 0.535 mg/kg/day for the first 3 weeks after transplantation protected all the recipients from developing GVHD up to 100 days after transplantation. PG490-88 inhibited in vivo both CD4+Vbeta3+ and CD8+Vbeta3+ T cell (alloreactive T cells in this model) expansion in the spleen by 64.09 and 34.02%, respectively, at the time when Vbeta3+ cell expansion was in the logarithmic phase (day 3 after transplantation). Intracellular cytokine staining without further in vitro activation demonstrated 47.42% inhibition of IL-2 production among CD4+ spleen cells in PG490-88-treated mice as compared to GVHD control on day 3 after transplantation. In contrast, CD25 (alpha chain of interleukin-2 receptor) expression did not differ. CONCLUSIONS: PG490-88 is highly effective in prevention of murine GVHD. The immunosuppressive effect of PG490-88 is mediated by inhibition of alloreactive T cell expansion through interleukin-2 production.

Duke Scholars

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Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

November 27, 2000

Volume

70

Issue

10

Start / End Page

1442 / 1447

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Surgery
  • Prodrugs
  • Mice, Inbred Strains
  • Mice, Inbred BALB C
  • Mice
  • Isoantibodies
  • Immunosuppressive Agents
  • Graft vs Host Disease
  • Diterpenes
 

Citation

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Chen, B. J., Liu, C., Cui, X., Fidler, J. M., & Chao, N. J. (2000). Prevention of graft-versus-host disease by a novel immunosuppressant, PG490-88, through inhibition of alloreactive T cell expansion. Transplantation, 70(10), 1442–1447. https://doi.org/10.1097/00007890-200011270-00008
Chen, B. J., C. Liu, X. Cui, J. M. Fidler, and N. J. Chao. “Prevention of graft-versus-host disease by a novel immunosuppressant, PG490-88, through inhibition of alloreactive T cell expansion.Transplantation 70, no. 10 (November 27, 2000): 1442–47. https://doi.org/10.1097/00007890-200011270-00008.
Chen BJ, Liu C, Cui X, Fidler JM, Chao NJ. Prevention of graft-versus-host disease by a novel immunosuppressant, PG490-88, through inhibition of alloreactive T cell expansion. Transplantation. 2000 Nov 27;70(10):1442–7.
Chen, B. J., et al. “Prevention of graft-versus-host disease by a novel immunosuppressant, PG490-88, through inhibition of alloreactive T cell expansion.Transplantation, vol. 70, no. 10, Nov. 2000, pp. 1442–47. Pubmed, doi:10.1097/00007890-200011270-00008.
Chen BJ, Liu C, Cui X, Fidler JM, Chao NJ. Prevention of graft-versus-host disease by a novel immunosuppressant, PG490-88, through inhibition of alloreactive T cell expansion. Transplantation. 2000 Nov 27;70(10):1442–1447.

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

November 27, 2000

Volume

70

Issue

10

Start / End Page

1442 / 1447

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Surgery
  • Prodrugs
  • Mice, Inbred Strains
  • Mice, Inbred BALB C
  • Mice
  • Isoantibodies
  • Immunosuppressive Agents
  • Graft vs Host Disease
  • Diterpenes