The form of allo-MHC class I antigen expressed by hepatocytes is critical in determining IL-2 responses by helper T cells

Background: Evidence suggests that liver transplants have immunosuppressive effects. It has been proposed that since hepatocytes produce significant a mounts of soluble MHC class I antigen, these molecules may have donor-speci fic immunosuppressive effects. Therefore, introduction of hepatocytes expre ssing donor-MHC antigen to potential organ recipients could promote subsequ ent allograft survival. To support this theory we have recently shown by in vivo gene transfer that soluble donor-MHC class I antigen can prolong live r allograft survival. Interestingly, we also have data that suggests one po ssible mechanism of this effect could relate to donor-soluble MHC antigen i nhibition of helper T cell IL-2 production. Aim: Since liver transplantation involves introduction of hepatocytes that express relatively large amounts of membrane-bound donor MHC antigen, we pe rformed experiments here to determine if this non-soluble form of the antig en also reduces IL-2 responses by helper T-cells. Methods: Lewis (RT1.A(1)) rats were injected with syngeneic hepatocytes tra nsfected with plasmid DNA encoding the allogenic membrane-bound MHC class I antigen, RT 1.A(a). One day after injection, lymphocytes from spleen and l ymph node were tested in mixed lymphocyte cultures for their IL-2 response against ACI (RT1.A(a)) stimulator cells. Results: In contrast to our previous findings, where soluble allo-MHC molec ules suppressed the IL-2 response by helper T-cells, the membrane-bound for m failed to decrease IL-2 production. Moreover, the membrane-bound alloanti gen significantly stimulated an increase in IL-2 secretion. Conclusion: Our data suggests that although soluble forms of donor-MHC anti gen may have immunosuppressive properties, exposure of potential organ tran splant recipients to hepatocytes expressing membrane-bound forms of the sam e antigen may increase the risk for immunologic sensitization.