Journal ArticleDOI
An essential role for Scurfin in CD4+CD25+ T regulatory cells.
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TLDR
It is shown that Foxp3 is highly expressed by TR cells and is associated with TR cell activity and phenotype, indicating that the Scurfin and CTLA-4 pathways may intersect and providing further insight into the TR cell lineage.Abstract:
The molecular properties that characterize CD4+CD25+ regulatory T cells (TR cells) remain elusive. Absence of the transcription factor Scurfin (also known as forkhead box P3 and encoded by Foxp3) causes a rapidly fatal lymphoproliferative disease, similar to that seen in mice lacking cytolytic T lymphocyte-associated antigen 4 (CTLA-4). Here we show that Foxp3 is highly expressed by T(R) cells and is associated with T(R) cell activity and phenotype. Scurfin-deficient mice lack T(R) cells, whereas mice that overexpress Foxp3 possess more T(R) cells. In Foxp3-overexpressing mice, both CD4+CD25- and CD4-CD8+ T cells show suppressive activity and CD4+CD25- cells express glucocorticoid-induced tumor-necrosis factor receptor-related (GITR) protein. The forced expression of Foxp3 also delays disease in CTLA-4-/- mice, indicating that the Scurfin and CTLA-4 pathways may intersect and providing further insight into the T(R) cell lineage.read more
Citations
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Journal ArticleDOI
Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells.
Estelle Bettelli,Yijun Carrier,Wenda Gao,Thomas Korn,Terry B. Strom,Mohamed Oukka,Howard L. Weiner,Vijay K. Kuchroo +7 more
TL;DR: It is shown that IL-6, an acute phase protein induced during inflammation, completely inhibits the generation of Foxp3+ Treg cells induced by TGF-β, and the data demonstrate a dichotomy in thegeneration of pathogenic (TH17) T cells that induce autoimmunity and regulatory (Foxp3+) T Cells that inhibit autoimmune tissue injury.
Journal ArticleDOI
Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival.
Tyler J. Curiel,George Coukos,Linhua Zou,Xavier Alvarez,Pui Cheng,Peter Mottram,Melina Evdemon-Hogan,Jose R. Conejo-Garcia,Lin Zhang,Matthew E. Burow,Yun Zhu,Shuang Wei,Ilona Kryczek,Ben Daniel,Alan N. Gordon,Leann Myers,Andrew A. Lackner,Mary L. Disis,Keith L. Knutson,Lieping Chen,Weiping Zou +20 more
TL;DR: It is shown, in detailed studies of CD4+CD25+FOXP3+ Treg cells in 104 individuals affected with ovarian carcinoma, that human tumor T Reg cells suppress tumor-specific T cell immunity and contribute to growth of human tumors in vivo.
Journal ArticleDOI
Conversion of Peripheral CD4+CD25− Naive T Cells to CD4+CD25+ Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3
Wanjun Chen,Wenwen Jin,Neil J. Hardegen,Ke Jian Lei,Li Li,Nancy J. Marinos,George McGrady,Sharon M. Wahl +7 more
TL;DR: Novel evidence is presented that conversion of naive peripheral CD4+CD25− T cells into anergic/suppressor cells that are CD25+, CD45RB−/low and intracellular CTLA-4+ can be achieved through costimulation with T cell receptors (TCRs) and transforming growth factor β (TGF-β).
Journal ArticleDOI
Regulatory T Cells and Immune Tolerance
TL;DR: The cellular and molecular basis of Treg development and function is revealed and dysregulation of T Regs in immunological disease is implicates.
Journal ArticleDOI
Toll-like receptor control of the adaptive immune responses.
Akiko Iwasaki,Ruslan Medzhitov +1 more
TL;DR: Recognition of microbial infection and initiation of host defense responses is controlled by multiple mechanisms and recent studies have provided important clues about the mechanisms of TLR-mediated control of adaptive immunity orchestrated by dendritic cell populations in distinct anatomical locations.
References
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Journal ArticleDOI
The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3.
Craig L. Bennett,Jacinda R. Christie,Fred Ramsdell,Mary E. Brunkow,Polly J. Ferguson,Luke Whitesell,Thaddeus E. Kelly,Frank T. Saulsbury,Phillip F. Chance,Hans D. Ochs +9 more
TL;DR: Genetic evidence is presented that different mutations of the human gene FOXP3, the ortholog of the gene mutated in scurfy mice (Foxp3), causes IPEX syndrome.
Journal ArticleDOI
Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease
Marcia M. Shull,Ilona Ormsby,Ann B. Kier,Sharon A. Pawlowski,Ronald J. Diebold,Moying Yin,Ruth D. Allen,Charles L. Sidman,Gabriele Proetzel,Dawn Calvin,Nikki Annunziata,Thomas Doetschman +11 more
TL;DR: TGF-β1-deficient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions.
Journal ArticleDOI
Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4
Paul Waterhouse,Josef M. Penninger,Emma Timms,Andrew Wakeham,Arda Shahinian,Kelvin P. Lee,Craig B. Thompson,Henrik Griesser,Tak W. Mak +8 more
TL;DR: Although CTLA-4-deficient T cells proliferated spontaneously and strongly when stimulated through the T cell receptor, they were sensitive to cell death induced by cross-linking of the Fas receptor and by gamma irradiation, and is vital for the control of lymphocyte homeostasis.
Journal ArticleDOI
Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4
Elizabeth A. Tivol,Frank Borriello,A N Schweitzer,W P Lynch,Jeffrey A. Bluestone,Arlene H. Sharpe +5 more
TL;DR: In this article, the authors showed that CTLA-4-deficient mice rapidly develop lymphoproliferative disease with multiorgan lymphocytic infiltration and tissue destruction, with particularly severe myocarditis and pancreatitis, and die by 3-4 weeks of age.
Journal ArticleDOI
Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse.
Mary E. Brunkow,Jeffery Ew,Hjerrild Ka,Bryan W. Paeper,L B Clark,Yasayko Sa,John E. Wilkinson,David J. Galas,Steven F. Ziegler,Fred Ramsdell +9 more
TL;DR: Genetic complementation demonstrates that the protein product of Foxp3, scurfin, is essential for normal immune homeostasis.