Modulation of immune responses after portal venous injection of antigen

Background. How the localization of antigen to the liver, through means suc h as oral ingestion, induces tolerance is poorly understood. Methods. To elucidate potential mechanisms we used an adoptive transfer sys tem wherein ova-specific T cells were infused into a syngeneic host, and an tigen-specific T-cell responses after delivery of soluble antigen into the liver were monitored. Results. After infusion of antigen into the portal vein, the frequency of a ntigen-specific T cells in lymph nodes draining the liver was lower than th e frequency in peripheral lymph nodes. These findings were the reverse of w hat is typically observed after subcutaneous injection of antigen with adju vant, Infusion of antigen with adjuvant into the portal vein did not alter this pattern of antigen-specific T-cell localization; however, an increased frequency of T cells, compared with antigen alone, was observed in periphe ral lymph nodes and spleen. After exposure to antigen via the portal vein, T cells isolated from lymph nodes draining the liver and challenged with an tigen in vitro exhibited a diminished proliferative response compared with T cells isolated from nondraining lymph nodes. This hyporesponsiveness was not observed when the antigen was administered with adjuvant, Conclusions. Our findings suggest that the influence of the liver on immune responses might reflect two processes: (1) loss of antigen-specific T cell s after primary antigen injection, and (2) hyporesponsiveness on reexposure to antigen. These mechanisms may contribute to the prevention of undesirab le immune responses to foods and enteric bacteria in the gastrointestinal t ract. Furthermore, these results underscore the importance of minimizing in flammation in circumstances such as islet transplantation, if endogenous me chanisms of tolerance induction are to be maximized.