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Int J Clin Exp Pathol 2013;6(2):116-123
Review Article
Advances in distinguishing natural from induced Foxp3+
regulatory T cells
Xiaohong Lin*, Maogen Chen*, Ya Liu, Zhiyong Guo, Xiaoshun He, David Brand, Song Guo Zheng
Organ Transplant center, 1st affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, P.R. China; Division
of Rheumatology and Immunology, Department of Medicine, University of Southern California, Keck School of
Medicine, Los Angeles, CA. 90033, USA; Division of Surgical, First affiliated Hospital of Shantou University, Shantou,
515041, P.R. China; Research Service, Veterans Affairs Medical Center, Memphis, USA. *Equal contributors.
Received October 28, 2012; Accepted November 16, 2012; Epub January 15, 2013; Published February 1, 2013
Abstract: For more than a decade now, the regulatory T (Treg) cell has widely been considered as a critical subpopulation
of T cells which can suppress effector T cell responses as well as suppressing the activity of other immune
cells, such as mast cell, dendritic cells, and B cells. Treg cells have been broadly characterized as comprising of two
main populations: thymus-derived natural Treg (nTreg) cells, and peripherally generated induced Treg (iTreg) cells.
Both subsets have similar phenotypic characteristics and comparable suppressive function against T cell-mediated
immune response and diseases. However, both Foxp3 positive Treg subsets exhibit some specific differences such
as different mRNA transcripts and protein expression, epigenetic modification, and stability. These subtle differences
reinforce the notion that they represent unique and distinct subsets. Accurately distinguishing iTregs from
nTregs will help to clarify the biological features and contributions of each Treg subsets in peripheral tolerance,
autoimmunity and tumor immunity. One difficult problem is that it has not been possible to distinguish iTregs from
nTregs using surface markers until two recent articles were published to address this possibility. This review will
focus on very recent advances in using molecular markers to differentiate these Treg subsets. (IJCEP1210016).
Keywords: Treg, Foxp3, Helios, Neuropilin 1
Address all correspondence to:
Dr. Song Guo Zheng
Division of Rheumatology and Immunology
University of Southern California,
2011 Zonal Avenue, HMR 711, Los Angeles, CA 90033, USA.
Phone: 323 4422128; Fax: 323 4422874
E-mail: szheng@usc.edu.
Dr. Xiaoshun He,
Organ Transplant center
1st affiliated Hospital of Sun Yat-sen University
Guangzhou, 510080, P.R. China.
Tel: +86 20 87306082; Fax: +86 20 87306082
E-mail: gdtrc@163.com
Review Article
Advances in distinguishing natural from induced Foxp3+
regulatory T cells
Xiaohong Lin*, Maogen Chen*, Ya Liu, Zhiyong Guo, Xiaoshun He, David Brand, Song Guo Zheng
Organ Transplant center, 1st affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, P.R. China; Division
of Rheumatology and Immunology, Department of Medicine, University of Southern California, Keck School of
Medicine, Los Angeles, CA. 90033, USA; Division of Surgical, First affiliated Hospital of Shantou University, Shantou,
515041, P.R. China; Research Service, Veterans Affairs Medical Center, Memphis, USA. *Equal contributors.
Received October 28, 2012; Accepted November 16, 2012; Epub January 15, 2013; Published February 1, 2013
Abstract: For more than a decade now, the regulatory T (Treg) cell has widely been considered as a critical subpopulation
of T cells which can suppress effector T cell responses as well as suppressing the activity of other immune
cells, such as mast cell, dendritic cells, and B cells. Treg cells have been broadly characterized as comprising of two
main populations: thymus-derived natural Treg (nTreg) cells, and peripherally generated induced Treg (iTreg) cells.
Both subsets have similar phenotypic characteristics and comparable suppressive function against T cell-mediated
immune response and diseases. However, both Foxp3 positive Treg subsets exhibit some specific differences such
as different mRNA transcripts and protein expression, epigenetic modification, and stability. These subtle differences
reinforce the notion that they represent unique and distinct subsets. Accurately distinguishing iTregs from
nTregs will help to clarify the biological features and contributions of each Treg subsets in peripheral tolerance,
autoimmunity and tumor immunity. One difficult problem is that it has not been possible to distinguish iTregs from
nTregs using surface markers until two recent articles were published to address this possibility. This review will
focus on very recent advances in using molecular markers to differentiate these Treg subsets. (IJCEP1210016).
Keywords: Treg, Foxp3, Helios, Neuropilin 1
Address all correspondence to:
Dr. Song Guo Zheng
Division of Rheumatology and Immunology
University of Southern California,
2011 Zonal Avenue, HMR 711, Los Angeles, CA 90033, USA.
Phone: 323 4422128; Fax: 323 4422874
E-mail: szheng@usc.edu.
Dr. Xiaoshun He,
Organ Transplant center
1st affiliated Hospital of Sun Yat-sen University
Guangzhou, 510080, P.R. China.
Tel: +86 20 87306082; Fax: +86 20 87306082
E-mail: gdtrc@163.com
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