Induction of indirect donor-specific hyporesponsiveness by transportal RT1-peptide pulse in rat skin transplantation.
In the present study, we examined whether transportal pulse of class I major histocompatibility complex (MHC) allopeptides can induce indirect (non-chimeric) donor-specific hyporesponsiveness, using a high-responder rat skin transplantation model. Two donor-specific 8-amino acid peptides corresponding to residues 58-65 and 70-77 in the alpha(1) helical region of RT1.A(a) were synthesized. In order to test immunogenicity of these peptides, mixed lymphocyte reaction (MLR) was performed. Then, 100-microg portions of peptides were injected into recipient Lewis (LEW, RT1.A(l)) rats via the portal vein 14 days before skin transplantation. Skin allografts from August Copenhagen Irish (ACI, RT1(a)) or Wistar King A (WKA, RT1(k), third-party) donors were transplanted to LEW (RT1(l)) recipients. Transportal pulse of residues 58-65 and 70-77 prolonged graft survival significantly in ACI-to-LEW skin transplantation (17.6+/-0.40 and 18.0+/-0.45 days) compared with control (14.2+/-0.37 days). However, pulse of residues 106-113, a non-donor-specific control, did not prolong graft survival time (14.6+/-0.40 days) in the same combination. Regarding the third-party donor, residues 58-65 injected into LEW recipients had no effect on survival time of skin grafts (19.0+/-0.84 days) derived from WKA donors compared with the untreated WKA-to-LEW control (19.4+/-0.93 days). Transportal pulse of RT1.A(a) peptides induced donor-specific hyporesponsiveness even in a high-responder rat skin transplantation model. Our results suggest that graft enhancement by transportal exposure to donor cells may not be induced by a chimeric process but, instead, by an indirect mechanism not involving intervention of viable donor cells.
Division of Abdominal Transplantation, Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, 700-8558 Okayama, Japan.
Masao
M
Yamamura
Takahito
T
Yagi
Hiromi
H
Iwagaki
Naoshi
N
Mitsuoka
Liu
L
Jie
Sun Dong
SD
Sheng
Hiroaki
H
Matsuda
Hiroshi
H
Sadamori
Masaru
M
Inagaki
Noriaki
N
Tanaka
D000595:Amino Acid Sequence; D000818:Animals; D006084:Graft Rejection / Q000276:immunology; D006649:Histocompatibility Antigens / Q000737:chemistry* / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D016038:Skin Transplantation / Q000276:immunology*; D014019:Tissue Donors; D014184:Transplantation, Homologous
D006649:Histocompatibility Antigens; C038353:histocompatibility antigens RT, rat