Anti-histone H1 Autoantibody: An Inducible Immunosuppressive Factor in Liver Transplantation

In a rat model of tolerogeneic liver transplantation, set-Urn from the recipient has been shown to exhibit a strong immunosuppressive activity. However, molecular identify 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 H1. Polyclonal antibody raised against histone H I 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 H1 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 CIDIIb(+) monocytes/macrophages. These results raise a possibility that 16G9 may suppress MLR via cross-reaction with target antigens on the leukocytes.