The role of ICAM-1 in the induction of antigen-specific T cell hyporesponsiveness

We have previously demonstrated that pre-transplant transfusion of allogeneic splenic mononuclear cells from B10.BR mice to C3H/HeJ recipient mice resulted in subsequent antigen specific skin graft prolongation and an associated predominance of IL-4-producing T lymphocytes. In this report, we examined the role of ICAM-1 in the induction of T cell hyporesponsiveness and skin graft prolongation following intrahepatic alloantigen delivery. C3H/HeJ mice receiving splenic cells from B10.BR mice intrahepatically showed antigen-specific enhanced skin graft survival. This graft survival was further prolonged following pre-treatment of infused cells with anti-ICAM-1. No such prolongation was seen following intravenous administration of cells in the presence or absence of anti-ICAM-1 pre-treatment. Anti-ICAM-1 infusion alone similarly had no effect when given intrahepatically or peripherally. T lymphocytes from the mice receiving intrahepatic splenic cells and anti-ICAM-1 produced significantly higher amounts of IL-4 compared to mice receiving intrahepatic cells alone or intravenous cells. PCR analysis of ICAM-1 mRNA transcripts demonstrated an increased expression of ICAM-1 in the spleen compared to the liver. These results suggest that ICAM-1 plays an important role in the induction of T cell hyporesponsiveness and allograft prolongation following the intrahepatic encounter of alloantigen.