Low-dose IL-2 for in vivo expansion of CD4+ and CD8+ regulatory T cells in nonhuman primates

A. Aoyama, D. Klarin, Y. Yamada, S. Boskovic, O. Nadazdin, K. Kawai, D. Schoenfeld, J. C. Madsen, A. B. Cosimi, G. Benichou, T. Kawai

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15 Citations (Scopus)

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. Low-dose IL-2 therapy significantly expands functional CD4+ and CD8 + regulatory T cells in the peripheral blood with limited expansion of non-Treg cells in nonhuman primates.

Original languageEnglish
Pages (from-to)2532-2537
Number of pages6
JournalAmerican Journal of Transplantation
Volume12
Issue number9
DOIs
Publication statusPublished - 2012 Sep 1
Externally publishedYes

Keywords

  • Immunotherapy
  • T-regulatory cells
  • interleukin-2
  • nonhuman primates

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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    Aoyama, A., Klarin, D., Yamada, Y., Boskovic, S., Nadazdin, O., Kawai, K., Schoenfeld, D., Madsen, J. C., Cosimi, A. B., Benichou, G., & Kawai, T. (2012). Low-dose IL-2 for in vivo expansion of CD4+ and CD8+ regulatory T cells in nonhuman primates. American Journal of Transplantation, 12(9), 2532-2537. https://doi.org/10.1111/j.1600-6143.2012.04133.x