Thymic generation and selection of CD25+CD4+ regulatory T cells

Implications of their broad repertoire and high self-reactivity for the maintenance of immunological self-tolerance

Shimon Sakaguchi, Shohei Hori, Yoshinori Fukui, Takehiko Sasazuki, Noriko Sakaguchi, Takeshi Takahashi, Bach

Research output: Contribution to journalReview article

33 Citations (Scopus)

Abstract

Besides positive and negative selection of T cells, another function of the thymus in maintaining immunological self-tolerance is the production of CD25+CD4+ regulatory T cells capable of preventing autoimmune disease. They acquire the regulatory activity through the thymic selection process, and are released to the periphery as a functionally and phenotypically mature population. Our recent study with transgenic mice in which every class II MHC molecule covalently binds the same single peptide has revealed that a particular self-peptide/MHC ligand in the thymus can positively select a broad repertoire of functionally mature CD25+CD4+ regulatory T cells as well as naïve T cells. Interestingly, the regulatory T cells bear higher reactivity than other T cells to the selecting ligand in the thymus even after negative selection by the ligand. This broad repertoire and high self-reactivity of CD25+CD4+ regulatory T cells, together with their high level expression of various accessory molecules, may guarantee their prompt and efficient activation upon encounter with a diverse range of self peptide/MHC complexes in the periphery, ensuring dominant control of self-reactive T cells.

Original languageEnglish
Pages (from-to)6-23
Number of pages18
JournalNovartis Foundation symposium
Volume252
Publication statusPublished - Dec 1 2003

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Self Tolerance
Regulatory T-Lymphocytes
Thymus Gland
T-Lymphocytes
Ligands
Peptides
Transgenic Mice
Autoimmune Diseases
Population

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Thymic generation and selection of CD25+CD4+ regulatory T cells : Implications of their broad repertoire and high self-reactivity for the maintenance of immunological self-tolerance. / Sakaguchi, Shimon; Hori, Shohei; Fukui, Yoshinori; Sasazuki, Takehiko; Sakaguchi, Noriko; Takahashi, Takeshi; Bach.

In: Novartis Foundation symposium, Vol. 252, 01.12.2003, p. 6-23.

Research output: Contribution to journalReview article

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abstract = "Besides positive and negative selection of T cells, another function of the thymus in maintaining immunological self-tolerance is the production of CD25+CD4+ regulatory T cells capable of preventing autoimmune disease. They acquire the regulatory activity through the thymic selection process, and are released to the periphery as a functionally and phenotypically mature population. Our recent study with transgenic mice in which every class II MHC molecule covalently binds the same single peptide has revealed that a particular self-peptide/MHC ligand in the thymus can positively select a broad repertoire of functionally mature CD25+CD4+ regulatory T cells as well as na{\"i}ve T cells. Interestingly, the regulatory T cells bear higher reactivity than other T cells to the selecting ligand in the thymus even after negative selection by the ligand. This broad repertoire and high self-reactivity of CD25+CD4+ regulatory T cells, together with their high level expression of various accessory molecules, may guarantee their prompt and efficient activation upon encounter with a diverse range of self peptide/MHC complexes in the periphery, ensuring dominant control of self-reactive T cells.",
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AU - Takahashi, Takeshi

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