Anti-histone HI Autoantibody: An Inducible Immunosuppressive Factor in Liver Transplantation

摘要

In a rat model of tolerogeneic liver transplantation, serum from the recipient has been shown to exhibit a strong immunosuppressive activity. However, molecular identity of those humoral factors has yet to be elucidated. We previously found that one of major immunosuppressive factors in the recipient serum was transplantation-induced IgG antibodies. Here we identified an antigen recognized by the regulatory IgG as histone HI. Polyclonal antibody raised against histone HI not only suppressed allogeneic mixed lymphocyte reaction (MLR), but also prolonged allograft survival in vivo. To elucidate mechanisms underlying the immunosuppressive activity, we generated murine anti-histone HI monoclonal antibodies (mAbs) which can suppress allogeneic MLR. One of selected mAbs, termed 16G9, showed a dose-dependent MLR inhibitory activity. Flow cytometric analysis revealed that 16G9 specifically reacted with a part of murine splenocytes including T cells, B cells, and CD1 lb~+ monocytes/macrophages. These results raise a possibility that 16G9 may suppress MLR via cross-reaction with target antigens on the leukocytes.