Induction of oral tolerance and the effect of interleukin-4 on murine skin allograft rejection.
We studied the effect of oral and portal vein administration of alloantigens on mouse skin allograft survival. Graft receptor BALB/c mice received spleen cells (30, 90, 150 or 375 x 10(6)) from donor C57BL/6 mice intragastrically on three successive days, starting seven days before the skin graft. Allograft survival was significantly increased with the feeding of 150 x 10(6) allogeneic spleen cells by one gavage (median survival of 12 vs 14 days, P< or =0.005) or when 300 x 10(6) cells were given in six gavage (12 vs 14 days, P<0.04). A similar effect was observed when 150 x 10(6) spleen cells were injected into the portal vein (12 vs 14 days, P< or =0.03). Furthermore, prolonged allograft survival was observed with subcutaneous (12 vs 16 days, P< or =0.002) or systemic (12 vs 15 days, P< or =0.016) application of murine interleukin-4 (IL-4), alone or in combination with spleen cell injection into the portal vein (12 vs 18 days, P< or =0.0018). Taken together, these results showed that tolerance induction with spleen cells expressing fully incompatible antigens by oral administration or intraportal injection partially down-modulates skin allograft rejection. Furthermore, these findings demonstrated for the first time the effect of subcutaneous or systemic IL-4 application on allograft skin survival suggesting its use as a beneficial support therapy in combination with a tolerance induction protocol.
Dettino
A L A
AL
Laboratório de Alergia e Imunologia Clínica e Experimental, LIM-56, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
Duarte
A J S
AJ
Sato
M N
MN
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D017690:Cell Transplantation / Q000379:methods*; D006085:Graft Survival / Q000276:immunology*; D007275:Injections, Intravenous; D015847:Interleukin-4 / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011169:Portal Vein; D016038:Skin Transplantation / Q000276:immunology*; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous
D000276:Adjuvants, Immunologic; D015847:Interleukin-4