Different immune effects on cardiac allografts and xenografts induced by neonatal intrathymic inoculation with allogeneic and xenogeneic antigens.
BACKGROUND
In a previous study we demonstrated that intrathymic exposure of neonatal rats to both alloantigens and xenoantigens produced tolerance only to subsequent cardiac allografts and not to xenografts implanted when the animals were 6 weeks old. Interestingly, graft recipients were not sensitized to the xenografts as observed in the adult model. This study was designed to investigate whether earlier grafting would produce tolerance to cardiac xenografts in animals pretreated by neonatal intrathymic inoculation with allogeneic and xenogeneic cells.


METHODS
All recipient animals were Lewis rats. Donors were either Lewis Brown Norway rats or Golden Syrian hamsters. Lewis Brown Norway rat and hamster splenocytes (25 x 10(6) cells in a volume of 0.01 ml) were inoculated percutaneously into the thymus of neonatal recipients (n = 22). At age 4 weeks, five pretreated recipients underwent cervical heterotopic heart transplantation with rat hearts, and 2 weeks later abdominal heterotopic transplantation was done with hamster donors. A second group ( n = 6) received hamster hearts as the first graft and then grafts from rat donors. The third group underwent rat followed by hamster heart transplantation at age 6 to 7 weeks.


RESULTS
Mean rat allograft survival time for groups 1,2, and 3, respectively was 49.8 days with 4 of 5 surviving indefinitely, 4.3 days with 2 of 3 surviving indefinitely, and 42 days with 7 of 11 surviving indefinitely (p < 0.01 versus untreated control animals, 7.8 days, n = 5). In rats undergoing transplantation at 4 weeks, cardiac xenografts were rejected in 2.5 days 2.3 days, which was significantly shorter than xenograft survival (3.3 days) in rats that underwent transplantation at an older age (p < 0.02), in naive rats (p < 0.05), and in rats treated with hamster cells alone (p < 0.05). Mixed lymphocyte reaction showed a diminished proliferative response to Lewis Brown Norway rat cells in pretreated rats, which retained the ability to respond in culture to hamster cells (p < 0.05).


CONCLUSIONS
Earlier grafting in rats pretreated as neonates produces allograft tolerance but may accelerate rejection of xenografts. Preliminary mixed lymphocyte reaction results suggest that only the alloimmune cellular proliferative response is abrogated by this pretreatment.
Shen
Z
Z
Department of Cardiothoracic Surgery, Medical College of Pennsylvania, Philadelphia. USA.
Pelletier
S
S
Mohiuddin
M
M
Yokoyama
H
H
Reiss
G R
GR
DiSesa
V J
VJ
D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000008:administration & dosage; D017690:Cell Transplantation; D006224:Cricetinae; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D007108:Immune Tolerance; D007959:Lymphocyte Culture Test, Mixed; D008647:Mesocricetus; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland; D014183:Transplantation, Heterologous / Q000276:immunology*; D016042:Transplantation, Heterotopic / Q000276:immunology; D014184:Transplantation, Homologous
D000941:Antigens