Administration of a CD31-derived peptide delays the onset and significantly increases survival from lethal graft-versus-host disease.
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.
Chen
Y
Y
Department of Medicine, Stanford University Medical Center, CA 94305, USA.
Schlegel
P G
PG
Tran
N
N
Thompson
D
D
Zehnder
J L
JL
Chao
N J
NJ
D000595:Amino Acid Sequence; D000818:Animals; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D006183:H-2 Antigens / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000737:chemistry / Q000502:physiology*; D011828:Radiation Chimera; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
D006183:H-2 Antigens; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D019408:Platelet Endothelial Cell Adhesion Molecule-1