Liver sinusoidal endothelial cells contribute to alloreactive T-cell tolerance induced by portal venous injection of donor splenocytes.
We demonstrated that an indirect pathway of alloantigen presentation via liver sinusoidal endothelial cells (LSEC) is involved in alloreactive T-cell tolerance induced by portal venous injection (PI) of donor cells. Thirty million C57BL/6 (B6) splenocytes that were either untreated or treated with 30-Gy irradiation were injected via the portal vein into Balb/c mice. Host LSEC expressing major histocompatibility complex class II actively endocytosed the allogeneic naive splenocytes as well as irradiated splenocytes after PI. Using a transendothelial migration assay, it was demonstrated that host-type Balb/c CD4(+) T cells that transmigrated across LSEC that had captured irradiated B6 splenocytes were rendered tolerant to subsequent alloantigen presentation by host professional antigen-presenting cells. Consistently, PI of irradiated donor-type splenocytes led to remarkable prolongation of the survival of subsequently transplanted heart allografts. These results indicate that indirect antigen presentation by LSEC significantly contributes to alloreactive T-cell tolerance induced by PI of irradiated donor splenocytes.
Tokita
Daisuke
D
Department of Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi, Minami-Ku, Hiroshima, Japan.
Ohdan
Hideki
H
Onoe
Takashi
T
Hara
Hidetaka
H
Tanaka
Yuka
Y
Asahara
Toshimasa
T
D000818:Animals; D017951:Antigen Presentation; D004705:Endocytosis; D042783:Endothelial Cells / Q000276:immunology; D005260:Female; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology; D022781:Hepatocytes / Q000276:immunology*; D007108:Immune Tolerance; D007519:Isoantigens; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011169:Portal Vein; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D013601:T-Lymphocytes / Q000276:immunology*; D014019:Tissue Donors; D014184:Transplantation, Homologous
D007519:Isoantigens