Prolongation of heart xenograft survival in a hamster-to-rat model after therapy with a rationally designed immunosuppressive peptide
Brouard, S.; Cuturi, M.C.; Pignon, P.; Buelow, R.; Loth, P.; Moreau, A.; Soulillou, J.P.
Transplantation 67(12): 1614-1618
1999
ISSN/ISBN: 0041-1337 PMID: 10401770 Document Number: 506940
Background. Modification of the aminoacid sequence of peptides derived from the HLA class I heavy chain in combination with computer rational design resulted in the development of a peptide, RDP1258, with enhanced immunosuppressive activity. Methods. We evaluated the activity of this peptide, analyzing infiltrate by immunohistology and cytokine transcripts by reverse transcriptase-polymerase chain reaction method, in a hamster-to-rat xenograft model where recipients were treated with cobra venom factor (CVF) and peptide. Results. Although CVF or peptide alone had no effect, a combination of CVF/peptide RDP1258 resulted in a significant prolongation of graft survival (7.9+-1 vs. 4.5+-0 and 3.5+-0 days, P<0.001). This effect was associated with an increased expression of heme oxygenase 1 (HO-1) in spleen, a significant reduced graft infiltrate, and a decrease of tumor necrosis factor-alpha mRNA transcripts (P<0.05) compared with CVF-treated recipients (1.6+-0.07 vs. 3.3+-0.3%, P=0.001) on day 3 after transplantation. Conclusion. These observations are consistent with the observation that up-regulation of HO-1 results in inhibition of immune effector functions and suggest that the peptide acts, at least partially, through HO-1 regulation.