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Regulatory T-cells
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 Classics
 Phenotypic and functional identification

The first paper that directly showed depletion of a particular T cell subpopulation can break natural self-tolerance and cause a variety of autoimmune diseases in mice similar to their human counterparts. Transfer of CD5lo cells into nude (nu/nu) mice induced autoimmunity, whereas transfer of CD5hi cells did not. Transfer of both subsets together prevented disease. The CD5hi cells were subsequently shown to be CD25+ Treg cells. This work demonstrated that suppression can be a mechanism of preventing autoimmune disease.

Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease.
Sakaguchi, S., Fukuma, K., Kuribayashi, K. & Masuda, T.
Pubmed

The first experimental evidence of the existence of a subset (CD45RBlo) of peripheral CD4+ T cells that negatively regulates CD4+ effector T cells.

OX-22high CD4+ T cells induce wasting disease with multiple organ pathology: prevention by the OX-22low subset.
Powrie, F. & Mason, D.
Pubmed

The identification of CD25 as a marker of natural Treg cells and initial characterization of the function of CD25+CD4+ Treg cells returned credibility to the idea of suppression. This work allowed the field to focus on the same subset of cells.

Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.
Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M. & Toda, M.
Pubmed

Two papers reporting a simple in vitro assay for Treg cell function, making it possible to analyze Treg cells in rodents and humans. These were also the first papers to present an extensive characterization of Treg cell properties in vitro.

Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state.
Takahashi, T., Kuniyasu, Y., Toda, M., Sakaguchi, N., Itoh, M., Iwata, M., Shimizu, J. & Sakaguchi, S.
Pubmed
CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production.
Thornton, A. M. & Shevach, E. M
Pubmed

Identification of GITR as a potential marker of Treg cells.

CD4+CD25+ immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor.
McHugh, R.S., Whitters, M.J., Piccirillo, C.A., Young, D.A., Shevach, E.M., Collins, M. & Byrne, M.C.
Pubmed

Three papers showing Foxp3, encoding a member of the forkhead transcription factor family, is a 'master control gene' for the development and function of natural CD4+CD25+ Treg cells. This work also indicated that abnormality in Treg cells can be a cause of human autoimmune disease, allergy and inflammatory bowel disease, as in the human syndrome IPEX.

Control of regulatory T cell development by the transcription factor Foxp3
Hori, S., Nomura, T. & Sakaguchi, S.
Pubmed
Foxp3 programs the development and function of CD4+CD25+ regulatory T cells.
Fontenot, J.D., Gavin, M.A. & Rudensky, A.Y.
Abstract | Full text | PDF
An essential role for Scurfin in CD4+CD25+ T regulatory cells.
Khattri, R., Cox, T., Yasayko, S.A. & Ramsdell, F.
Abstract | Full text | PDF

The dynamics of in vivo Treg cell suppression.

In vivo dynamics of antigen-specific regulatory T cells not predicted from behavior in vitro
Klein, L., Khazaie, K. & von Boehmer, H.
Pubmed
 
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Nature Immunology
ISSN: 1529-2908
EISSN: 1529-2916
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