Published in J Exp Med on November 21, 2005
Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity (2008) 6.08
Regulatory T cells sequentially migrate from inflamed tissues to draining lymph nodes to suppress the alloimmune response. Immunity (2009) 3.32
Human T regulatory cell therapy: take a billion or so and call me in the morning. Immunity (2009) 3.21
Altering the distribution of Foxp3(+) regulatory T cells results in tissue-specific inflammatory disease. J Exp Med (2007) 3.17
Pathogen-specific regulatory T cells delay the arrival of effector T cells in the lung during early tuberculosis. J Exp Med (2010) 2.35
How punctual ablation of regulatory T cells unleashes an autoimmune lesion within the pancreatic islets. Immunity (2009) 2.15
TCR-based lineage tracing: no evidence for conversion of conventional into regulatory T cells in response to a natural self-antigen in pancreatic islets. J Exp Med (2007) 2.15
Dendritic cells with TGF-beta1 differentiate naive CD4+CD25- T cells into islet-protective Foxp3+ regulatory T cells. Proc Natl Acad Sci U S A (2007) 2.10
A central role for induced regulatory T cells in tolerance induction in experimental colitis. J Immunol (2009) 2.01
Foxp3+ regulatory T cells maintain immune homeostasis in the skin. J Exp Med (2008) 1.85
The defect in T-cell regulation in NOD mice is an effect on the T-cell effectors. Proc Natl Acad Sci U S A (2008) 1.85
Regulatory T cells and inhibitory cytokines in autoimmunity. Curr Opin Immunol (2009) 1.79
Loss of epigenetic modification driven by the Foxp3 transcription factor leads to regulatory T cell insufficiency. Immunity (2012) 1.61
Enhancing the in vivo expansion of adoptively transferred EBV-specific CTL with lymphodepleting CD45 monoclonal antibodies in NPC patients. Blood (2008) 1.52
Enhanced thymic selection of FoxP3+ regulatory T cells in the NOD mouse model of autoimmune diabetes. Proc Natl Acad Sci U S A (2007) 1.51
CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis. Proc Natl Acad Sci U S A (2011) 1.47
Anti-CD3 therapy permits regulatory T cells to surmount T cell receptor-specified peripheral niche constraints. J Exp Med (2010) 1.41
Expansion of Th17 cells and functional defects in T regulatory cells are key features of the pancreatic lymph nodes in patients with type 1 diabetes. Diabetes (2011) 1.39
PSG9 Stimulates Increase in FoxP3+ Regulatory T-Cells through the TGF-β1 Pathway. PLoS One (2016) 1.39
In vivo sites and cellular mechanisms of T reg cell-mediated suppression. J Exp Med (2006) 1.37
Adoptive regulatory T-cell therapy protects against cerebral ischemia. Ann Neurol (2013) 1.30
CD40Ig treatment results in allograft acceptance mediated by CD8CD45RC T cells, IFN-gamma, and indoleamine 2,3-dioxygenase. J Clin Invest (2007) 1.23
Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Curr Diabetes Rev (2013) 1.21
The IL-2/CD25 pathway determines susceptibility to T1D in humans and NOD mice. J Clin Immunol (2008) 1.19
Treg cells, life history, and diversity. Cold Spring Harb Perspect Biol (2012) 1.19
Apoptosis of CD4+ CD25(high) T cells in type 1 diabetes may be partially mediated by IL-2 deprivation. PLoS One (2009) 1.19
Organ-specific and memory treg cells: specificity, development, function, and maintenance. Front Immunol (2014) 1.11
Regulatory T cell migration during an immune response. Trends Immunol (2012) 1.10
T-cell exhaustion: understanding the interface of chronic viral and autoinflammatory diseases. Immunol Cell Biol (2016) 1.08
Regulatory T cells in experimental autoimmune disease. Springer Semin Immunopathol (2006) 1.06
Real-time immune cell interactions in target tissue during autoimmune-induced damage and graft tolerance. J Exp Med (2014) 1.05
Fetal regulatory T cells and peripheral immune tolerance in utero: implications for development and disease. Am J Reprod Immunol (2013) 1.04
A cluster of coregulated genes determines TGF-beta-induced regulatory T-cell (Treg) dysfunction in NOD mice. Proc Natl Acad Sci U S A (2011) 1.03
Excessive Th1 responses due to the absence of TGF-β signaling cause autoimmune diabetes and dysregulated Treg cell homeostasis. Proc Natl Acad Sci U S A (2013) 1.02
Interindividual variation in human T regulatory cells. Proc Natl Acad Sci U S A (2014) 1.01
A novel pancreatic β-cell targeting bispecific-antibody (BsAb) can prevent the development of type 1 diabetes in NOD mice. Clin Immunol (2014) 1.01
Expanded nonhuman primate tregs exhibit a unique gene expression signature and potently downregulate alloimmune responses. Am J Transplant (2008) 1.00
Viral infection prevents diabetes by inducing regulatory T cells through NKT cell-plasmacytoid dendritic cell interplay. J Exp Med (2011) 0.97
An early age-related increase in the frequency of CD4+ Foxp3+ cells in BDC2.5NOD mice. Immunology (2007) 0.96
Following the fate of one insulin-reactive CD4 T cell: conversion into Teffs and Tregs in the periphery controls diabetes in NOD mice. Diabetes (2012) 0.96
Roles for cathepsins S, L, and B in insulitis and diabetes in the NOD mouse. J Autoimmun (2009) 0.94
IL-2: a two-faced master regulator of autoimmunity. J Autoimmun (2011) 0.93
T cell-driven initiation and propagation of autoimmune diabetes. Curr Opin Immunol (2011) 0.92
Treatment with MOG-DNA vaccines induces CD4+CD25+FoxP3+ regulatory T cells and up-regulates genes with neuroprotective functions in experimental autoimmune encephalomyelitis. J Neuroinflammation (2012) 0.92
The B10 Idd9.3 locus mediates accumulation of functionally superior CD137(+) regulatory T cells in the nonobese diabetic type 1 diabetes model. J Immunol (2012) 0.92
Pathogenic CD4⁺ T cells recognizing an unstable peptide of insulin are directly recruited into islets bypassing local lymph nodes. J Exp Med (2013) 0.92
High-throughput sequencing of islet-infiltrating memory CD4+ T cells reveals a similar pattern of TCR Vβ usage in prediabetic and diabetic NOD mice. PLoS One (2013) 0.92
A censored beta mixture model for the estimation of the proportion of non-differentially expressed genes. Bioinformatics (2010) 0.91
Targeting of myelin protein zero in a spontaneous autoimmune polyneuropathy. J Immunol (2008) 0.91
Regulation of multi-organ inflammation in the regulatory T cell-deficient scurfy mice. J Biomed Sci (2009) 0.91
Homeostasis and function of regulatory T cells (Tregs) in vivo: lessons from TCR-transgenic Tregs. Immunol Rev (2014) 0.89
B1 cells promote pancreas infiltration by autoreactive T cells. J Immunol (2010) 0.89
Reduced IL-2 expression in NOD mice leads to a temporal increase in CD62Llo FoxP3+ CD4+ T cells with limited suppressor activity. Eur J Immunol (2011) 0.88
Tissue resident regulatory T cells: novel therapeutic targets for human disease. Cell Mol Immunol (2015) 0.87
Induction of self-antigen-specific Foxp3+ regulatory T cells in the periphery by lymphodepletion treatment with anti-mouse thymocyte globulin in mice. Immunology (2011) 0.86
IL-2/anti-IL-2 antibody complex treatment inhibits the development but not the progression of herpetic stromal keratitis. J Immunol (2014) 0.85
Regulation of type 1 diabetes, tuberculosis, and asthma by parasites. J Mol Med (Berl) (2009) 0.85
The cellular prion protein is preferentially expressed by CD4+ CD25+ Foxp3+ regulatory T cells. Immunology (2008) 0.85
Regulatory T cells fail to suppress CD4T+-bet+ T cells in relapsing multiple sclerosis patients. Immunology (2008) 0.85
Expression level of a pancreatic neo-antigen in beta cells determines degree of diabetes pathogenesis. J Autoimmun (2010) 0.84
Restricted autoantigen recognition associated with deletional and adaptive regulatory mechanisms. J Immunol (2009) 0.84
CD122+CD8+ Treg suppress vaccine-induced antitumor immune responses in lymphodepleted mice. Eur J Immunol (2010) 0.84
Immune tolerance induction by integrating innate and adaptive immune regulators. Cell Transplant (2009) 0.84
Long-term control of alloreactive B cell responses by the suppression of T cell help. J Immunol (2008) 0.83
Therapeutic regulatory T cells subvert effector T cell function in inflamed islets to halt autoimmune diabetes. J Immunol (2015) 0.82
PLG scaffold delivered antigen-specific regulatory T cells induce systemic tolerance in autoimmune diabetes. Tissue Eng Part A (2013) 0.82
Foxp3(+) regulatory T cells in mouse models of type 1 diabetes. J Diabetes Res (2013) 0.82
Infiltrative T regulatory cells in enucleated uveal melanomas. Trans Am Ophthalmol Soc (2009) 0.82
Expression of regulatory T cell (Treg) activation markers in endometrial tissues from early and late pregnancy in the feline immunodeficiency virus (FIV)-infected cat. Placenta (2010) 0.81
Inhibition of Fas ligand in NOD mice unmasks a protective role for IL-10 against insulitis development. Am J Pathol (2011) 0.81
Immunomodulation of antigen presenting cells promotes natural regulatory T cells that prevent autoimmune diabetes in NOD mice. PLoS One (2012) 0.81
Molecular mechanisms of regulatory T cell development. J Clin Immunol (2008) 0.81
Apoptosis of purified CD4+ T cell subsets is dominated by cytokine deprivation and absence of other cells in new onset diabetic NOD mice. PLoS One (2010) 0.81
Regulatory T cells for tolerance therapy: revisiting the concept. Crit Rev Immunol (2011) 0.81
Cathepsin L inhibition prevents murine autoimmune diabetes via suppression of CD8(+) T cell activity. PLoS One (2010) 0.80
Differential response of regulatory and conventional CD4⁺ lymphocytes to CD3 engagement: clues to a possible mechanism of anti-CD3 action? J Immunol (2013) 0.80
A combination dual-sized microparticle system modulates dendritic cells and prevents type 1 diabetes in prediabetic NOD mice. Clin Immunol (2015) 0.79
Advances and challenges in biomarker development for type 1 diabetes prediction and prevention using omic technologies. Expert Opin Med Diagn (2010) 0.79
Genetic control of the inflammatory T-cell response in regulatory T-cell deficient scurfy mice. Clin Immunol (2010) 0.79
Deficiency of foxp3 regulatory T cells exacerbates autoimmune arthritis by altering the synovial proportions of CD4 T cells and dendritic cells. Immune Netw (2011) 0.79
Selective elimination of autoreactive T cells in vivo by the regulatory T cells. Clin Immunol (2008) 0.79
Multimerized T cell epitopes protect from experimental autoimmune diabetes by inducing dominant tolerance. Proc Natl Acad Sci U S A (2007) 0.79
Type 1 diabetes genetic susceptibility and dendritic cell function: potential targets for treatment. J Leukoc Biol (2016) 0.78
Opposing effects of CTLA4 insufficiency on regulatory versus conventional T cells in autoimmunity converge on effector memory in target tissue. J Immunol (2014) 0.78
Engineered regulatory T cells coexpressing MHC class II:peptide complexes are efficient inhibitors of autoimmune T cell function and prevent the development of autoimmune arthritis. J Immunol (2013) 0.78
Placental immunopathology in the FIV-infected cat: a role for inflammation in compromised pregnancy? Vet Immunol Immunopathol (2009) 0.77
Are Regulatory T Cells Defective in Type 1 Diabetes and Can We Fix Them? J Immunol (2016) 0.76
Autoimmunity to type VII collagen in SKH1 mice is independent of regulatory T cells. Clin Exp Immunol (2006) 0.76
Altered connexin 43 expression underlies age-dependent decrease of regulatory T cell suppressor function in nonobese diabetic mice. J Immunol (2015) 0.76
The Biology of Autoimmune Response in the Scurfy Mice that Lack the CD4+Foxp3+ Regulatory T-Cells. Biology (Basel) (2012) 0.76
Singular role for T-BET+CXCR3+ regulatory T cells in protection from autoimmune diabetes. Proc Natl Acad Sci U S A (2016) 0.75
Exploring the induction of preproinsulin-specific Foxp3(+) CD4(+) Treg cells that inhibit CD8(+) T cell-mediated autoimmune diabetes by DNA vaccination. Sci Rep (2016) 0.75
Unsupervised assessment of microarray data quality using a Gaussian mixture model. BMC Bioinformatics (2009) 0.75
IL-2 as a therapeutic target for the restoration of Foxp3+ regulatory T cell function in organ-specific autoimmunity: implications in pathophysiology and translation to human disease. J Transl Med (2010) 0.75
Type I diabetes-associated tolerogenic properties of interleukin-2. Clin Dev Immunol (2011) 0.75
Immunogenic, but not steady-state, antigen presentation permits regulatory T-cells to control CD8+ T-cell effector differentiation by IL-2 modulation. PLoS One (2014) 0.75
Deficiency of Nuclear Factor-κB c-Rel Accelerates the Development of Autoimmune Diabetes in NOD Mice. Diabetes (2016) 0.75
Thymic self-antigen expression for the design of a negative/tolerogenic self-vaccine against type 1 diabetes. Clin Dev Immunol (2011) 0.75
Expansion of FasL-Expressing CD5(+) B Cells in Type 1 Diabetes Patients. Front Immunol (2017) 0.75
B cell-targeted immunotherapy for type 1 diabetes: What can make it work? Discov Med (2016) 0.75
Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol (2003) 38.57
Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity (2005) 23.00
Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med (2004) 22.96
Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol (2004) 17.40
B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity (2000) 15.44
Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet (2001) 14.15
CD4+ CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol (2002) 12.73
In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J Exp Med (2004) 8.00
Regulatory T cells in the control of immune pathology. Nat Immunol (2001) 6.98
A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol (2005) 6.77
Following a diabetogenic T cell from genesis through pathogenesis. Cell (1993) 6.46
CD4+CD25+ T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms. J Exp Med (2003) 6.00
Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivo. Nat Immunol (2001) 5.95
Mechanisms of suppression by suppressor T cells. Nat Immunol (2005) 5.52
Developmental stage, phenotype, and migration distinguish naive- and effector/memory-like CD4+ regulatory T cells. J Exp Med (2004) 5.08
Naive T cells transiently acquire a memory-like phenotype during homeostasis-driven proliferation. J Exp Med (2000) 5.07
Homeostasis-stimulated proliferation drives naive T cells to differentiate directly into memory T cells. J Exp Med (2000) 4.54
CD25+ CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes. J Exp Med (2004) 4.35
In vivo dynamics of antigen-specific regulatory T cells not predicted from behavior in vitro. Proc Natl Acad Sci U S A (2003) 4.18
Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo. Proc Natl Acad Sci U S A (2004) 4.12
CD25+ CD4+ T cells regulate the expansion of peripheral CD4 T cells through the production of IL-10. J Immunol (2001) 4.07
Initiation of autoimmune diabetes by developmentally regulated presentation of islet cell antigens in the pancreatic lymph nodes. J Exp Med (1999) 3.85
CD4+CD25+ T regulatory cells dependent on ICOS promote regulation of effector cells in the prediabetic lesion. J Exp Med (2004) 3.57
CD25- T cells generate CD25+Foxp3+ regulatory T cells by peripheral expansion. J Immunol (2004) 3.36
TGF-beta regulates in vivo expansion of Foxp3-expressing CD4+CD25+ regulatory T cells responsible for protection against diabetes. Proc Natl Acad Sci U S A (2004) 3.26
Recruitment of Foxp3+ T regulatory cells mediating allograft tolerance depends on the CCR4 chemokine receptor. J Exp Med (2005) 3.17
Physiological beta cell death triggers priming of self-reactive T cells by dendritic cells in a type-1 diabetes model. J Exp Med (2003) 2.94
A role for CD103 in the retention of CD4+CD25+ Treg and control of Leishmania major infection. J Immunol (2005) 2.81
CD40 ligation releases immature dendritic cells from the control of regulatory CD4+CD25+ T cells. Immunity (2003) 2.59
Pancreatic lymph node-derived CD4(+)CD25(+) Treg cells: highly potent regulators of diabetes that require TRANCE-RANK signals. Immunity (2002) 2.20
T cell regulation as a side effect of homeostasis and competition. J Exp Med (2003) 2.15
Pancreatic islet-specific T-cell clones from nonobese diabetic mice. Proc Natl Acad Sci U S A (1989) 2.12
Susceptible MHC alleles, not background genes, select an autoimmune T cell reactivity. J Clin Invest (2003) 1.80
Regulatory T-cell therapy: is it ready for the clinic? Nat Rev Immunol (2005) 1.76
Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells. J Clin Invest (2004) 1.74
Antigen-specific FoxP3-transduced T-cells can control established type 1 diabetes. Diabetes (2004) 1.73
Damage control, rather than unresponsiveness, effected by protective DX5+ T cells in autoimmune diabetes. Nat Immunol (2001) 1.67
CD4+CD25+ cells controlling a pathogenic CD4 response inhibit cytokine differentiation, CXCR-3 expression, and tissue invasion. J Immunol (2004) 1.66
Regulation of diabetes development by regulatory T cells in pancreatic islet antigen-specific TCR transgenic nonobese diabetic mice. J Immunol (2002) 1.39
Leukocyte attraction through the CCR5 receptor controls progress from insulitis to diabetes in non-obese diabetic mice. Eur J Immunol (2004) 1.12
Transcription factors in autoimmunity. Curr Opin Immunol (2003) 0.85
Projection of an immunological self shadow within the thymus by the aire protein. Science (2002) 12.15
Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med (2009) 9.71
FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell (2006) 9.24
Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity (2010) 8.90
The AKT-mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells. J Exp Med (2008) 6.07
Gut immune maturation depends on colonization with a host-specific microbiota. Cell (2012) 5.91
Mast cells: a cellular link between autoantibodies and inflammatory arthritis. Science (2002) 5.82
Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. Immunity (2007) 5.67
Arthritis critically dependent on innate immune system players. Immunity (2002) 5.31
Cytokine requirements for acute and Basal homeostatic proliferation of naive and memory CD8+ T cells. J Exp Med (2002) 5.09
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PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature (2012) 4.31
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CD4+CD25+ T regulatory cells dependent on ICOS promote regulation of effector cells in the prediabetic lesion. J Exp Med (2004) 3.57
Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice. Proc Natl Acad Sci U S A (2011) 3.55
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Retinoic acid enhances Foxp3 induction indirectly by relieving inhibition from CD4+CD44hi Cells. Immunity (2008) 3.25
How antibodies to a ubiquitous cytoplasmic enzyme may provoke joint-specific autoimmune disease. Nat Immunol (2002) 3.20
Antigen persistence is required throughout the expansion phase of a CD4(+) T cell response. J Exp Med (2005) 3.14
A special population of regulatory T cells potentiates muscle repair. Cell (2013) 3.09
A comprehensive review of interventions in the NOD mouse and implications for translation. Immunity (2005) 3.07
Critical roles for interleukin 1 and tumor necrosis factor alpha in antibody-induced arthritis. J Exp Med (2002) 2.98
Physiological beta cell death triggers priming of self-reactive T cells by dendritic cells in a type-1 diabetes model. J Exp Med (2003) 2.94
Number of T reg cells that differentiate does not increase upon encounter of agonist ligand on thymic epithelial cells. J Exp Med (2004) 2.92
Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity. Immunity (2011) 2.87
Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire. J Exp Med (2007) 2.84
Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells. Proc Natl Acad Sci U S A (2006) 2.83
Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes. Science (2014) 2.77
Aire's partners in the molecular control of immunological tolerance. Cell (2010) 2.68
Self-reactivity in thymic double-positive cells commits cells to a CD8 alpha alpha lineage with characteristics of innate immune cells. Nat Immunol (2004) 2.68
A decade of AIRE. Nat Rev Immunol (2007) 2.45
Islet recovery and reversal of murine type 1 diabetes in the absence of any infused spleen cell contribution. Science (2006) 2.38
Genomic definition of multiple ex vivo regulatory T cell subphenotypes. Proc Natl Acad Sci U S A (2010) 2.30
How punctual ablation of regulatory T cells unleashes an autoimmune lesion within the pancreatic islets. Immunity (2009) 2.15
TCR-based lineage tracing: no evidence for conversion of conventional into regulatory T cells in response to a natural self-antigen in pancreatic islets. J Exp Med (2007) 2.15
Regulatory T cells: recommendations to simplify the nomenclature. Nat Immunol (2013) 2.13
Particularities of the vasculature can promote the organ specificity of autoimmune attack. Nat Immunol (2006) 2.12
Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging. Nat Immunol (2012) 2.11
Rituximab specifically depletes short-lived autoreactive plasma cells in a mouse model of inflammatory arthritis. Proc Natl Acad Sci U S A (2010) 2.09
Modifier loci condition autoimmunity provoked by Aire deficiency. J Exp Med (2005) 2.08
Endocrine self and gut non-self intersect in the pancreatic lymph nodes. Proc Natl Acad Sci U S A (2005) 2.06
Natural killer cells distinguish innocuous and destructive forms of pancreatic islet autoimmunity. Proc Natl Acad Sci U S A (2004) 1.96
Arthritogenic monoclonal antibodies from K/BxN mice. J Exp Med (2002) 1.94
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Noninvasive imaging of pancreatic islet inflammation in type 1A diabetes patients. J Clin Invest (2010) 1.93
Genetic inversion in mast cell-deficient (Wsh) mice interrupts corin and manifests as hematopoietic and cardiac aberrancy. Am J Pathol (2008) 1.93
A multiply redundant genetic switch 'locks in' the transcriptional signature of regulatory T cells. Nat Immunol (2012) 1.93
Back to central tolerance. Immunity (2004) 1.88
The defect in T-cell regulation in NOD mice is an effect on the T-cell effectors. Proc Natl Acad Sci U S A (2008) 1.85
Mast cells contribute to initiation of autoantibody-mediated arthritis via IL-1. Proc Natl Acad Sci U S A (2007) 1.84
Aire employs a histone-binding module to mediate immunological tolerance, linking chromatin regulation with organ-specific autoimmunity. Proc Natl Acad Sci U S A (2008) 1.83