Literature DB >> 22682297

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

A Aoyama1, D Klarin, Y Yamada, S Boskovic, O Nadazdin, K Kawai, D Schoenfeld, J C Madsen, A B Cosimi, G Benichou, T Kawai.   

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. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

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Year:  2012        PMID: 22682297      PMCID: PMC3429727          DOI: 10.1111/j.1600-6143.2012.04133.x

Source DB:  PubMed          Journal:  Am J Transplant        ISSN: 1600-6135            Impact factor:   8.086


  19 in total

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Journal:  Cancer Res       Date:  2007-08-01       Impact factor: 12.701

Review 2.  Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases.

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3.  Massive ex vivo expansion of human natural regulatory T cells (T(regs)) with minimal loss of in vivo functional activity.

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Journal:  Sci Transl Med       Date:  2011-05-18       Impact factor: 17.956

4.  Pathological and clinical correlates of FOXP3+ cells in renal allografts during acute rejection.

Authors:  F Veronese; S Rotman; R N Smith; T D Pelle; M L Farrell; T Kawai; A Benedict Cosimi; R B Colvin
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Review 5.  CD4+ T-regulatory cells: toward therapy for human diseases.

Authors:  Sarah E Allan; Raewyn Broady; Silvia Gregori; Megan E Himmel; Natasha Locke; Maria Grazia Roncarolo; Rosa Bacchetta; Megan K Levings
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6.  IL-2 induces in vivo suppression by CD4(+)CD25(+)Foxp3(+) regulatory T cells.

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7.  Interleukin-2 therapy in patients with HIV infection.

Authors:  D Abrams; Y Lévy; M H Losso; A Babiker; G Collins; D A Cooper; J Darbyshire; S Emery; L Fox; F Gordin; H C Lane; J D Lundgren; R Mitsuyasu; J D Neaton; A Phillips; J P Routy; G Tambussi; D Wentworth
Journal:  N Engl J Med       Date:  2009-10-15       Impact factor: 91.245

8.  In vivo expansion of naive and activated CD4+CD25+FOXP3+ regulatory T cell populations in interleukin-2-treated HIV patients.

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Review 9.  Treatment of metastatic melanoma: an overview.

Authors:  Shailender Bhatia; Scott S Tykodi; John A Thompson
Journal:  Oncology (Williston Park)       Date:  2009-05       Impact factor: 2.990

10.  Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor.

Authors:  Makoto Miyara; Yumiko Yoshioka; Akihiko Kitoh; Tomoko Shima; Kajsa Wing; Akira Niwa; Christophe Parizot; Cécile Taflin; Toshio Heike; Dominique Valeyre; Alexis Mathian; Tatsutoshi Nakahata; Tomoyuki Yamaguchi; Takashi Nomura; Masahiro Ono; Zahir Amoura; Guy Gorochov; Shimon Sakaguchi
Journal:  Immunity       Date:  2009-05-21       Impact factor: 31.745

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  11 in total

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Review 2.  Cytokine Signaling in the Development and Homeostasis of Regulatory T cells.

Authors:  Kevin H Toomer; Thomas R Malek
Journal:  Cold Spring Harb Perspect Biol       Date:  2018-03-01       Impact factor: 10.005

3.  Dose-finding/phase II trial: bevacizumab, immunotherapy, and chemotherapy (BIC) in metastatic renal cell cancer (mRCC). Antitumor effects and variations of circulating T regulatory cells (Treg).

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Journal:  Target Oncol       Date:  2014-09-19       Impact factor: 4.493

Review 4.  The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases.

Authors:  David Klatzmann; Abul K Abbas
Journal:  Nat Rev Immunol       Date:  2015-04-17       Impact factor: 53.106

5.  Repeated Injections of IL-2 Break Renal Allograft Tolerance Induced via Mixed Hematopoietic Chimerism in Monkeys.

Authors:  Y Yamada; O Nadazdin; S Boskovic; S Lee; E Zorn; R N Smith; R B Colvin; J C Madsen; A B Cosimi; T Kawai; G Benichou
Journal:  Am J Transplant       Date:  2015-07-17       Impact factor: 8.086

6.  Combined GM-CSF and G-CSF administration mobilizes CD4+ CD25hi Foxp3hi Treg in leukapheresis products of rhesus monkeys.

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Journal:  Am J Transplant       Date:  2020-01-20       Impact factor: 8.086

7.  Impact of Human Mutant TGFβ1/Fc Protein on Memory and Regulatory T Cell Homeostasis Following Lymphodepletion in Nonhuman Primates.

Authors:  H Guo; L Lu; R Wang; A Perez-Gutierrez; H S Abdulkerim; A F Zahorchak; T L Sumpter; K A Reimann; A W Thomson; M B Ezzelarab
Journal:  Am J Transplant       Date:  2016-07-11       Impact factor: 8.086

8.  Human and Mouse CD8(+)CD25(+)FOXP3(+) Regulatory T Cells at Steady State and during Interleukin-2 Therapy.

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Journal:  Front Immunol       Date:  2015-04-15       Impact factor: 7.561

9.  Sustained in vivo signaling by long-lived IL-2 induces prolonged increases of regulatory T cells.

Authors:  Charles J M Bell; Yongliang Sun; Urszula M Nowak; Jan Clark; Sarah Howlett; Marcin L Pekalski; Xin Yang; Oliver Ast; Inja Waldhauer; Anne Freimoser-Grundschober; Ekkehard Moessner; Pablo Umana; Christian Klein; Ralf J Hosse; Linda S Wicker; Laurence B Peterson
Journal:  J Autoimmun       Date:  2014-10-30       Impact factor: 7.094

10.  Herbal Components of a Novel Formula PSORI-CM02 Interdependently Suppress Allograft Rejection and Induce CD8+CD122+PD-1+ Regulatory T Cells.

Authors:  Chuanjian Lu; Huazhen Liu; Xiaowei Jin; Yuchao Chen; Chun-Ling Liang; Feifei Qiu; Zhenhua Dai
Journal:  Front Pharmacol       Date:  2018-02-12       Impact factor: 5.810

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