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Liver sinusoidal endothelial cells contribute to alloreactive T-cell tolerance induced by portal venous injection of donor splenocytes.

Tokita D, Ohdan H, Onoe T, Hara H, Tanaka Y, Asahara T

Department of Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi, Minami-Ku, Hiroshima, Japan.

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.

Published 4 February 2005 in Transpl Int, 18(2): 237-45.
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