Allogeneic neonatal blood transfusion without recipient preconditioning is a novel strategy to treat autoimmune diabetes in NOD mice

Abstract

The efficacy of neonatal blood derived from diabetes‐resistant mice to reverse autoimmune diabetes was evaluated in NOD mice under irradiation‐free and immunosuppression‐free conditions. Transfusion of allogeneic neonatal blood containing Sca‐1+ pluripotential stem/progenitor cells significantly delayed the onset and incidence of diabetes. Neonatal blood transfusion also reduced the mononuclear cell infiltration of the islets of Langerhans. Flow cytometry and RT‐PCR analysis revealed the induction of chimerism in neonatal blood transfused NOD mice. Splenocytes from most cured NOD mice failed to transfer diabetes into immunodeficient NODscid mice, indicating deletion/suppression of diabetogenic T cells in transfused mice. Protection afforded by neonatal blood transfusion was not simply due to alterations in T regulatory subsets. Splenic T cells from both cured and unprotected mice that received neonatal blood transfusion proliferated poorly and produced lower amounts of IL‐2 and IL‐17A when challenged with allogeneic antigens in vitro. These data indicate that neonatal blood transfusion can serve as a novel strategy to induce lymphoid chimerism, T cell tolerance and deletion/suppression of diabetogenic T cells in the absence of cytoreduction or costimulatory blockade.