Journal ArticleDOI
CTLA-4 Control over Foxp3+ Regulatory T Cell Function
Kajsa Wing,Yasushi Onishi,Yasushi Onishi,Paz Prieto-Martin,Tomoyuki Yamaguchi,Makoto Miyara,Zoltan Fehervari,Takashi Nomura,Shimon Sakaguchi,Shimon Sakaguchi +9 more
TLDR
It is shown that a specific deficiency of cytotoxic T lymphocyte antigen 4 (CTLA-4) in Tregs results in spontaneous development of systemic lymphoproliferation, fatal T cell–mediated autoimmune disease, and hyperproduction of immunoglobulin E in mice.Abstract:
Naturally occurring Foxp3+CD4+ regulatory T cells (Tregs) are essential for maintaining immunological self-tolerance and immune homeostasis. Here, we show that a specific deficiency of cytotoxic T lymphocyte antigen 4 (CTLA-4) in Tregs results in spontaneous development of systemic lymphoproliferation, fatal T cell-mediated autoimmune disease, and hyperproduction of immunoglobulin E in mice, and it also produces potent tumor immunity. Treg-specific CTLA-4 deficiency impairs in vivo and in vitro suppressive function of Tregs-in particular, Treg-mediated down-regulation of CD80 and CD86 expression on dendritic cells. Thus, natural Tregs may critically require CTLA-4 to suppress immune responses by affecting the potency of antigen-presenting cells to activate other T cells.read more
Citations
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The blockade of immune checkpoints in cancer immunotherapy
TL;DR: Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
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Cancer immunotherapy comes of age
TL;DR: In the context of advances in the understanding of how tolerance, immunity and immunosuppression regulate antitumour immune responses, these successes suggest that active immunotherapy represents a path to obtain a durable and long-lasting response in cancer patients.
Journal ArticleDOI
Immune checkpoint blockade: a common denominator approach to cancer therapy
TL;DR: The immune system recognizes and is poised to eliminate cancer but is held in check by inhibitory receptors and ligands, so drugs interrupting immune checkpoints, such as anti-CTLA-4, anti-PD-1, and others in early development, can unleash anti-tumor immunity and mediate durable cancer regressions.
Journal ArticleDOI
Regulatory T Cells: Mechanisms of Differentiation and Function
TL;DR: Cellular and molecular mechanisms in the differentiation and function of regulatory T cells and their role in autoimmune and autoinflammatory disorders, allergy, acute and chronic infections, cancer, and metabolic inflammation are discussed.
Journal ArticleDOI
Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota
Koji Atarashi,Takeshi Tanoue,Kenshiro Oshima,Wataru Suda,Yuji Nagano,Hiroyoshi Nishikawa,Shinji Fukuda,Takuro Saito,Seiko Narushima,Koji Hase,Sangwan Kim,Joëlle V. Fritz,Paul Wilmes,Satoshi Ueha,Kouji Matsushima,Hiroshi Ohno,Bernat Olle,Shimon Sakaguchi,Tadatsugu Taniguchi,Hidetoshi Morita,Masahira Hattori,Kenya Honda +21 more
TL;DR: Using a rational approach to isolate CD4+FOXP3+ regulatory T (Treg)-cell-inducing bacterial strains from the human indigenous microbiota may allow for tailored therapeutic manipulation of human immune disorders.
References
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Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
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TL;DR: This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest.
Journal ArticleDOI
Control of Regulatory T Cell Development by the Transcription Factor Foxp3
TL;DR: Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells and retroviral gene transfer of Foxp3 converts naïve T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+.
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
Enhancement of antitumor immunity by CTLA-4 blockade.
TL;DR: In vivo administration of antibodies to CTLA-4 resulted in the rejection of tumors, including preestablished tumors, and this rejection resulted in immunity to a secondary exposure to tumor cells, suggesting that blockade of the inhibitory effects of CTLA4 can allow for, and potentiate, effective immune responses against tumor cells.
Journal ArticleDOI
The Wellcome Trust Case Control Consortium, U.K.
TL;DR: This article reports that the magazine's award for Research Leader of the Year was given to the Wellcome Trust Case Control Consortium which conducted a huge genetic study to look at the genetic causes for various diseases.
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F. Stephen Hodi,Steven J. O'Day,David F. McDermott,R. W. Weber,Jeffrey A. Sosman,John B. A. G. Haanen,Rene Gonzalez,Caroline Robert,Dirk Schadendorf,Jessica C. Hassel,Wallace Akerley,Alfons J.M. van den Eertwegh,Jose Lutzky,Paul Lorigan,Julia Vaubel,Gerald P. Linette,David W. Hogg,Christian H. Ottensmeier,Céleste Lebbé,Christian Peschel,Ian Quirt,Joseph I. Clark,Jedd D. Wolchok,Jeffrey S. Weber,Jason Tian,Michael Yellin,Geoffrey M. Nichol,Axel Hoos,Walter J. Urba +28 more