[Induction of skin immune tolerance of mouse to rat xenogeneic transplantation].
OBJECTIVE
To explore a moderate and effective project which will be clinically suitable to induce donor-specific tolerance across xenogeneic barriers.


METHODS
4 x 10(7) Lewis rat bone marrow cells were infused to 300 rad total body irradiated (TBI) C57BL/6 (B6) mice, combined with intraperitoneal administration of cyclophosphamide (CTX) and intravenous injection of anti-mouse CD4 monoclonal antibody. Recipient B6 mice were characterized for the tolerance status with donor Lewis rat skin graft, mixed lymphocyte reaction (MLR), and delayed-type hypersensitivity (DTH) assays after 30 days. Adoptive transfer and the effect of IL-2 on MLR were detected to further explore the tolerance mechanism.


RESULTS
Survival time of donor rat skin grafts was specifically prolonged in the tolerant B6 mice. The results of MLR and DTH assays showed donor-specific hyporeactivity, while the tolerant B6 mice were still immunocompetent to MHC-disparate third party BALB/c mouse or DA rat stimulator cells.


CONCLUSIONS
A reliable xenogeneic transplantation tolerance of mouse to rat was achieved by this project of tolerance induction. The result of in vitro and in vivo adoptive transfer of spleen cells from tolerant B6 mice demonstrated that the suppressor cells were unlikely to exert effect in the tolerance. The inhibition of specific MLR could be reversed by adding IL-2, indicating that clonal anergy instead of clonal deletion is responsible for the tolerant maintenance.
Song
X
X
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing 100083, China.
Huang
H
H
Hao
J
J
Xie
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D016026:Bone Marrow Transplantation; D015704:CD4 Antigens / Q000276:immunology; D003520:Cyclophosphamide / Q000494:pharmacology; D007108:Immune Tolerance / Q000187:drug effects / Q000528:radiation effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051381:Rats; D011917:Rats, Inbred Lew; D016038:Skin Transplantation / Q000276:immunology*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide