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Regulatory T Cells pp 3–17Cite as

Regulatory T Cells: History and Perspective

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 707))

Abstract

Despite the skepticism that once prevailed among immunologists, it is now widely accepted that the normal immune system harbors a T-cell population, called regulatory T cells (Treg cells), specialized for immune suppression. It was first shown that depletion of a T-cell subpopulation from normal rodents produced autoimmune disease. Search for a molecular marker specific for such autoimmune-preventive Treg cells has revealed that the majority, if not all, of them constitutively express the CD25 molecule as depletion of CD25+CD4+ T cells spontaneously evokes autoimmune disease in otherwise normal rodents. The expression of CD25 by Treg cells has made it possible to delineate their developmental pathways, in particular their thymic development, and establish simple in vitro assay for assessing their suppressive activity. The marker and the in vitro assay have helped to identify human Treg cells with similar functional and phenotypic characteristics. Recent efforts have shown that natural Treg cells specifically express the transcription factor Foxp3 and that mutations of the Foxp3 gene produce a variety of immunological diseases in humans and rodents. Specific expression of Foxp3 in natural Treg cells has enabled their functional and developmental characterization by genetic approach. These studies altogether have provided firm evidence for Foxp3+CD25+CD4+ Treg cells as an indispensable cellular constituent of the normal immune system for establishing and maintaining immunologic self-tolerance and immune homeostasis. Treg cells are now within the scope of clinical use to treat immunological diseases and control physiological and pathological immune responses.

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Abbreviations

APC:

Antigen-presenting cell

ATx:

Adult thymectomy

IBD:

Inflammatory bowel disease

IPEX:

Immune dysfunction, polyendocrinopathy, enteropathy, X-linked syndrome

NTx:

Neonatal thymectomy

T1D:

Type 1 diabetes mellitus

TCR:

T-cell receptor

Treg cells:

Regulatory T cells

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Acknowledgements

The author thanks Atsushi Tanaka for the critical reading of the manuscript. The author’s research is supported by grants-in-aid from the Ministry of Education, Science, Sports and Culture, and the Ministry of Human Welfare.

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Authors and Affiliations

  1. Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan

    Shimon Sakaguchi

  2. WPI Immunology Frontier Research Center, Osaka University, Suita, Japan

    Shimon Sakaguchi

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  1. Shimon Sakaguchi
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Editors and Affiliations

  1. , Division of Immunoregulation, MRC National Institute for Medical Resea, The Ridgeway, Mill Hill, London, NW7 1AA, United Kingdom

    George Kassiotis

  2. , VIB Autoimmune Genetics Laboratory, Katholieke Universiteit Leuven, Herestraat 49, Leuven, 3000, Belgium

    Adrian Liston

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Sakaguchi, S. (2011). Regulatory T Cells: History and Perspective. In: Kassiotis, G., Liston, A. (eds) Regulatory T Cells. Methods in Molecular Biology, vol 707. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61737-979-6_1

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  • DOI: https://doi.org/10.1007/978-1-61737-979-6_1

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