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

Research output: Contribution to journalArticle

14 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
Externally publishedYes

Fingerprint

Regulatory T-Lymphocytes
Primates
Interleukin-2
Organ Transplantation
Immunosuppressive Agents
Interleukin-1
Immunotherapy
Immunity
Acquired Immunodeficiency Syndrome
Therapeutics
Lymphocytes
T-Lymphocytes
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Aoyama, A., Klarin, D., Yamada, Y., Boskovic, S., Nadazdin, O., Kawai, K., ... 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

Low-dose IL-2 for in vivo expansion of CD4+ and CD8+ regulatory T cells in nonhuman primates. / Aoyama, A.; Klarin, D.; Yamada, Y.; Boskovic, S.; Nadazdin, O.; Kawai, K.; Schoenfeld, D.; Madsen, J. C.; Cosimi, A. B.; Benichou, G.; Kawai, T.

In: American Journal of Transplantation, Vol. 12, No. 9, 09.2012, p. 2532-2537.

Research output: Contribution to journalArticle

Aoyama, A, Klarin, D, Yamada, Y, Boskovic, S, Nadazdin, O, Kawai, K, Schoenfeld, D, Madsen, JC, Cosimi, AB, 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, vol. 12, no. 9, pp. 2532-2537. https://doi.org/10.1111/j.1600-6143.2012.04133.x
Aoyama, A. ; Klarin, D. ; Yamada, Y. ; Boskovic, S. ; Nadazdin, O. ; Kawai, K. ; Schoenfeld, D. ; Madsen, J. C. ; Cosimi, A. B. ; Benichou, G. ; Kawai, T. / Low-dose IL-2 for in vivo expansion of CD4+ and CD8+ regulatory T cells in nonhuman primates. In: American Journal of Transplantation. 2012 ; Vol. 12, No. 9. pp. 2532-2537.
@article{abcda4b02edc4a8bb633d6c9bd8cb0ee,
title = "Low-dose IL-2 for in vivo expansion of CD4+ and CD8+ regulatory T cells in nonhuman primates",
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 na{\"i}ve 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.",
keywords = "Immunotherapy, interleukin-2, nonhuman primates, T-regulatory cells",
author = "A. Aoyama and D. Klarin and Y. Yamada and S. Boskovic and O. Nadazdin and K. Kawai and D. Schoenfeld and Madsen, {J. C.} and Cosimi, {A. B.} and G. Benichou and T. Kawai",
year = "2012",
month = "9",
doi = "10.1111/j.1600-6143.2012.04133.x",
language = "English",
volume = "12",
pages = "2532--2537",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",
number = "9",

}

TY - JOUR

T1 - Low-dose IL-2 for in vivo expansion of CD4+ and CD8+ regulatory T cells in nonhuman primates

AU - Aoyama, A.

AU - Klarin, D.

AU - Yamada, Y.

AU - Boskovic, S.

AU - Nadazdin, O.

AU - Kawai, K.

AU - Schoenfeld, D.

AU - Madsen, J. C.

AU - Cosimi, A. B.

AU - Benichou, G.

AU - Kawai, T.

PY - 2012/9

Y1 - 2012/9

N2 - 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.

AB - 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.

KW - Immunotherapy

KW - interleukin-2

KW - nonhuman primates

KW - T-regulatory cells

UR - http://www.scopus.com/inward/record.url?scp=84865580488&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865580488&partnerID=8YFLogxK

U2 - 10.1111/j.1600-6143.2012.04133.x

DO - 10.1111/j.1600-6143.2012.04133.x

M3 - Article

C2 - 22682297

AN - SCOPUS:84865580488

VL - 12

SP - 2532

EP - 2537

JO - American Journal of Transplantation

JF - American Journal of Transplantation

SN - 1600-6135

IS - 9

ER -