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Administration of a CD31-derived peptide delays the onset and significantly
increases survival from lethal graft-versus-host disease
Y Chen, PG Schlegel, N Tran, D Thompson, JL Zehnder and NJ Chao
Department of Medicine, Stanford University Medical Center, CA 94305, USA.
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.
Volume 89,
Issue 4,
pp. 1452-1459,
02/15/1997
Copyright © 1997 by The American Society of Hematology
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