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Low‐Dose IL‐2 for In Vivo Expansion of CD4+ and CD8+ Regulatory T Cells in Nonhuman Primates
Authors:A Aoyama  D Klarin  Y Yamada  S Boskovic  O Nadazdin  K Kawai  D Schoenfeld  J C Madsen  A B Cosimi  G Benichou  T Kawai
Institution:1. Transplant Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA;2. Department of Biostatistics, Massachusetts General Hospital, Harvard Medical School, Boston, MA
Abstract:IL‐2 is a known potent T cell growth factor that amplifies lymphocyte responses in vivo. This capacity has led to the use of high‐dose IL‐2 to enhance T cell immunity in patients with AIDS or cancer. However, more recent studies have indicated that IL‐2 is also critical for the development and peripheral expansion of regulatory T cells (Tregs). In the current study, low‐dose IL‐2 (1 million IU/m2 BSA/day) was administered to expand Tregs in vivo in naïve nonhuman primates. Our study demonstrated that low‐dose IL‐2 therapy significantly expanded peripheral blood CD4+ and CD8+ Tregs in vivo with limited expansion of non‐Treg cells. These expanded Tregs are mainly CD45RA? Foxp3 high activated Tregs and demonstrated potent immunosuppressive function in vitro. The results of this preclinical study can serve as a basis to develop Treg immunotherapy, which has significant therapeutic potential in organ/cellular transplantation.
Keywords:Immunotherapy  interleukin‐2  nonhuman primates  T‐regulatory cells
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