Human Alpha1-Antitrypsin Therapy Synergizes with Temporary T Cell Depletion: Modified Repopulating T Cell Profile in Concordant and Discordant Xenoimmune Models

Introduction: T cells, primarily CD4+ cells, play a significant role in xenograft rejection. While temporary T cell depletion alone prolongs islet xenograft survival in mice, repopulating T cells acquire a profile that fails to achieve xenograft tolerance. Human α1-antitrypsin (AAT) is an anti-inflammatory and immunomodulatory molecule that allows undeterred purified T cell responses, resulting in, unlike classic immunosuppression, expansion of regulatory T cells (Tregs). Alone, AAT promotes islet allograft survival and fails to extend islet xenograft survival. In combination with temporary T cell depletion, AAT significantly promotes rat-to-mouse islet xenograft survival. The mechanism behind this synergy is unknown.