Evidence for Persistent Expression of OX2 as a Necessary Component of Prolonged Renal Allograft Survival Following Portal Vein Immunization

Following portal vein (pv) pretransplant immunization of C3H mice, there is an early (within 2 days) increase in expression of the molecule OX2 seen on host dendritic cells (DC), along with increased survival of C57BL/6 renal allografts transplanted within 24 h of pv immunization. In addition, there is a marked polarization in cytokine production from lymphocytes harvested from the transplanted animals, with preferential production of IL-4, IL-10, and TGFβ on donor-specific restimulation in vitro, and decreased production of IL-2, IFN-γ, and TNFα compared with non-pv-immunized control transplanted mice. Both the increased renal allograft survival and the altered cytokine production are abolished by infusion of anti-mouse OX2 monoclonal antibody (3B6), even when antibody infusion is begun as late as 10 days following transplantation. Quantitative PCR analysis independently shows that OX2 expression is increased in the spleen and liver of transplanted mice as late as 21 days following pv immunization. In vitro studies with an OX2:Fc immunoadhesion had suggested that immunosuppression induced by this soluble form of the OX2 molecule was dependent primarily upon an early (OX2-dependent) signal. This discrepancy between in vivo and in vitro data possibly reflects a role for OX2 in the in vivo recruitment of other (immunregulatory) cells. Consistent with this hypothesis, regardless of the time (posttransplantation) of in vivo infusion of anti-OX2 antibody, within 2 days we observed a decline in the functional activity of a previously characterized immunoregulatory γδTCR+ cell population, which can be monitored by its ability to regulate cytokine production in vitro.