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Background

Clinical application of islet transplantation to treat type 1 diabetes has been limited by islet allograft destruction by both allogeneic and autoimmune diabetogenic T-cell responses. The current study aims at determining whether an anti–T-cell receptor (TCR) monoclonal antibody (mAb) has potential as a novel and potent induction immunotherapy for islet transplantation.

Methods

We have investigated the therapeutic efficacy and mechanisms of action of anti-TCR therapy in four different murine models, which comprise either allo-or autoimmune responses alone or both together.

Results

T-cell response to islet allografts was potently abrogated by a brief treatment with an anti-TCRβ mAb (clone H57-597), resulting in long-term survival of BALB/c islet allografts in streptozotocin-induced diabetic B6 mice. Moreover, transient anti-TCR treatment permanently prevented BALB/c skin allograft rejection on Rag1 …