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

Am J Transplant. 2012 Sep;12(9):2532-7. doi: 10.1111/j.1600-6143.2012.04133.x. Epub 2012 Jun 8.

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/m(2) 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • Dose-Response Relationship, Drug
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / pharmacology*
  • Macaca fascicularis
  • Male
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Interleukin-2