Anti-histone HI Autoantibody Directly Acts on T Cells to Exert Its Immunosuppressive Activity

摘要

We previously demonstrated that histone HI-specific autoantibody is one of major immunosuppressive factors in a rat model of tolerogeneic liver transplantation. To gain insight into mechanisms underlying the tolerance induction, we generated a murineanti-histone HI monoclonal antibody (mAb) 16G9, that can block allogeneic mixed lymphocyte reaction. In the present study, we tested whether 16G9 mAb directly acts on T cells to exhibit immunosuppressive activity. 16G9 inhibited cell proliferation and EL-2 production of purified T cells upon stimulation with immobilized anti-CD3 antibody. 16G9 also suppressed pharmacological T cell activation bypassing T cell receptor (TCR) ligation, implying that 16G9 does not affect TCR-membrane proximal signaling event, but rather acts on downstream TCR signaling pathway to exert immunosuppressive activity. Flow cytometric analysis indicated that 16G9 specifically bound to a fraction of T cells. Exogenous addition of histone HI competitively inhibited the immunoreactivity, suggesting the existence of histone HI-like antigens on the T cell surface. Intriguingly, the 16G9-reactive T cell population was transiently increased upon TCR crosslinking, implicating that 16G9 might also react with activated T cells via inducible cross-reactive antigens.