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Administration of a CD31-derived peptide delays the onset and significantly increases survival from lethal graft-versus-host disease.

Publication ,  Journal Article
Chen, Y; Schlegel, PG; Tran, N; Thompson, D; Zehnder, JL; Chao, NJ
Published in: Blood
February 15, 1997

The CD31 monoclonal antibody, LYP21, binds to the CD31 domain 6 and inhibits the human mixed-lymphocyte reaction (MLR) in a specific and dose-dependent fashion. A synthetic CD31 peptide based on human CD31 epitope (amino acids 551 to 574) recognized by LYP21 is equally effective in inhibiting the MLR. In this study, we used the murine homolog of CD31 peptide 551 to 574 and a control peptide to study the role of CD31 molecule on T-cell activation. In vitro, CD31 peptide inhibited the MLR across several major and minor histocompatibility differences in a specific and dose-dependent fashion, similar to the results observed in the human system. Maximal inhibition was achieved at a dose of 200 microg/mL. In the cytotoxic T-lymphocyte (CTL) assay, CD31 peptide inhibited CTL responses by 97%. To study the in vivo effect of this peptide, graft-versus-host disease (GVHD) across minor histocompatibility barriers was induced in the B10.D2 (H-2d) --> BALB/c (H-2d) model. BALB/c recipients received CD31 peptide (100 microg/d), or phosphate-buffered saline (PBS), or control peptide (100 microg/d) intraperitoneally (IP) for the first 5 weeks. CD31 peptide delayed onset of graft-versus-host disease and significantly increased long-term survival. Twelve of 14 mice receiving CD31 peptide survived more than 100 days after transplantation, as compared with none of 10 mice receiving PBS and none of five mice receiving control peptide (P = .0001). Long-term engraftment of allogeneic bone marrow was documented in all transplanted mice by polymerase chain reaction (PCR) analysis of microsatellite region in the interleukin (IL)-1beta gene. Our data suggest that the CD31 molecule has an important functional role in T-cell activation in vitro and in vivo.

Duke Scholars

Published In

Blood

ISSN

0006-4971

Publication Date

February 15, 1997

Volume

89

Issue

4

Start / End Page

1452 / 1459

Location

United States

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • Radiation Chimera
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Peptide Fragments
  • Molecular Sequence Data
  • Mice, Inbred C57BL
  • Mice, Inbred C3H
  • Mice, Inbred BALB C
  • Mice
  • Lymphocyte Culture Test, Mixed
 

Citation

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MLA
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Chen, Y., Schlegel, P. G., Tran, N., Thompson, D., Zehnder, J. L., & Chao, N. J. (1997). Administration of a CD31-derived peptide delays the onset and significantly increases survival from lethal graft-versus-host disease. Blood, 89(4), 1452–1459.
Chen, Y., P. G. Schlegel, N. Tran, D. Thompson, J. L. Zehnder, and N. J. Chao. “Administration of a CD31-derived peptide delays the onset and significantly increases survival from lethal graft-versus-host disease.Blood 89, no. 4 (February 15, 1997): 1452–59.
Chen Y, Schlegel PG, Tran N, Thompson D, Zehnder JL, Chao NJ. Administration of a CD31-derived peptide delays the onset and significantly increases survival from lethal graft-versus-host disease. Blood. 1997 Feb 15;89(4):1452–9.
Chen Y, Schlegel PG, Tran N, Thompson D, Zehnder JL, Chao NJ. Administration of a CD31-derived peptide delays the onset and significantly increases survival from lethal graft-versus-host disease. Blood. 1997 Feb 15;89(4):1452–1459.

Published In

Blood

ISSN

0006-4971

Publication Date

February 15, 1997

Volume

89

Issue

4

Start / End Page

1452 / 1459

Location

United States

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • Radiation Chimera
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Peptide Fragments
  • Molecular Sequence Data
  • Mice, Inbred C57BL
  • Mice, Inbred C3H
  • Mice, Inbred BALB C
  • Mice
  • Lymphocyte Culture Test, Mixed