Infusion of donor hepatic non-parenchymal cells prolongs survival of skin allografts in mice: role of microchimerism and IL-4.
BACKGROUND
In the mouse skin allograft model, specific immune tolerance to the donor was induced by injection of donor hepatic non-parenchymal cells (NPCs). This markedly prolonged the survival time of the allograft. The mechanism of the induction of immune tolerance with donor hepatic NPCs is thought to be related to microchimerism and the IL-4 level. This work aimed at exploring the way of inducing immune tolerance and understanding the mechanism.


METHODS
C57BL/6 (B6) mice were primed by intravenous injection of 2 x 10(7) NPCs from C3H mice. Cyclophosphamide (200 mg/kg) was injected intraperitoneally 48 hours later. Eighteen days after the NPC injection, skin from C3H mice was transplanted to B6 mice and the survival of the grafts was assessed. The immune reaction of splenocytes from the treated B6 mice to donor-specific T-cells was measured by 3H-TdR incorporation. Microchimerism in the spleen was determined by flow cytometric analysis sytem (FCAS) analysis, and the serum level of IL-4 was assayed by ELISA at designed times.


RESULTS
The survival time of the skin graft was markedly prolonged from 10 days to 70 days in controls. Microchimerism in the spleen was found as early as day 1 post-NPC injection, then it increased steadily, and there was a positive relationship between graft survival and the quantity of microchimerism. The ELISA results showed that NPC infusion enhanced IL-4 production, especially in the mice with longer graft survival.


CONCLUSIONS
Donor NPC infusion pre-transplant can prolong the survival of the skin graft and microchimerism and high levels of IL-4 may be involved.
Ding
Xiao-Ming
XM
Department of Renal Transplantation, First Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China. xmding@medmail.com.cn
Xue
Wu-Jun
WJ
Ji
Zong-Zheng
ZZ
Tian
Pu-Xun
PX
D000818:Animals; D046528:Chimerism; D006085:Graft Survival / Q000276:immunology; D022781:Hepatocytes / Q000637:transplantation*; D007108:Immune Tolerance / Q000276:immunology*; D007275:Injections, Intravenous; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000097:blood; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D016038:Skin Transplantation / Q000276:immunology*
D015847:Interleukin-4