Mechanisms of autoimmunity in the non-obese diabetic mouse: effector/regulatory cell equilibrium during peak inflammation

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Mechanisms of autoimmunity in the non-obese diabetic mouse: effector/regulatory cell equilibrium during peak inflammation is …
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scholarly articleQ13442814

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P356DOI10.1111/IMM.12581
P932PMC publication ID4799883
P698PubMed publication ID26749404
P5875ResearchGate publication ID289970417

P2093author name stringNadir Askenasy
P2860cites workChronic antigen stimulation in vivo induces a distinct population of antigen-specific Foxp3 CD25 regulatory T cellsQ80139449
From vanilla to 28 flavors: multiple varieties of T regulatory cellsQ80141724
The insulin-specific T cells of nonobese diabetic mice recognize a weak MHC-binding segment in more than one formQ80257293
Perturbed homeostasis of peripheral T cells elicits decreased susceptibility to anti-CD3-induced apoptosis in prediabetic nonobese diabetic miceQ80597353
CD25- T cells generate CD25+Foxp3+ regulatory T cells by peripheral expansionQ81111400
Islet-specific expression of CXCL10 causes spontaneous islet infiltration and accelerates diabetes developmentQ81180071
Inducing and expanding regulatory T cell populations by foreign antigenQ81392563
CD4+CD25high regulatory T cells in human autoimmune diabetesQ81428869
Involvement of IL-2 in homeostasis of regulatory T cells: the IL-2 cycleQ81766038
Increased resistance to CD4+CD25hi regulatory T cell-mediated suppression in patients with type 1 diabetesQ82746957
Adaptive islet-specific regulatory CD4 T cells control autoimmune diabetes and mediate the disappearance of pathogenic Th1 cells in vivoQ83059341
IL-2 production by dendritic cells promotes Foxp3(+) regulatory T-cell expansion in autoimmune-resistant NOD congenic miceQ83228586
Killer Treg restore immune homeostasis and suppress autoimmune diabetes in prediabetic NOD miceQ83879823
Gld mutation of Fas ligand increases the frequency and up-regulates cell survival genes in CD25+CD4+ TR cellsQ83977704
CD25 shedding by human natural occurring CD4+CD25+ regulatory T cells does not inhibit the action of IL-2Q84064861
Intra-islet proliferation of cytotoxic T lymphocytes contributes to insulitis progressionQ84130770
Lymphopenia-induced spontaneous T-cell proliferation as a cofactor for autoimmune disease developmentQ84136013
Proinflammatory cytokines contribute to development and function of regulatory T cells in type 1 diabetesQ85492396
Stable activity of diabetogenic cells with age in NOD mice: dynamics of reconstitution and adoptive diabetes transfer in immunocompromised miceQ87409683
FOXP3 controls regulatory T cell function through cooperation with NFATQ24298179
Central role of defective interleukin-2 production in the triggering of islet autoimmune destructionQ24650734
Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3Q24672849
Identification of the beta cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes.Q24679680
Insulitis in human type 1 diabetes: a comparison between patients and animal modelsQ27023712
Control of regulatory T cell development by the transcription factor Foxp3Q27860489
Foxp3 programs the development and function of CD4+CD25+ regulatory T cellsQ27860714
Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseasesQ28131652
B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetesQ28143530
Multiple immuno-regulatory defects in type-1 diabetesQ28344695
A function for interleukin 2 in Foxp3-expressing regulatory T cellsQ28590646
Opinion: Satisfaction (not) guaranteed: re-evaluating the use of animal models of type 1 diabetesQ29393228
Phenotypic and functional features of human Th17 cellsQ29619323
Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic miceQ30498716
Early over expression of messenger RNA for multiple genes, including insulin, in the Pancreatic Lymph Nodes of NOD mice is associated with Islet AutoimmunityQ30874892
Pathogenic T-cell clones in autoimmune diabetes: more lessons from the NOD mouseQ33221766
At-risk and recent-onset type 1 diabetic subjects have increased apoptosis in the CD4+CD25+ T-cell fractionQ33268352
Apoptosis of CD4+ CD25(high) T cells in type 1 diabetes may be partially mediated by IL-2 deprivationQ33490627
Apoptosis of purified CD4+ T cell subsets is dominated by cytokine deprivation and absence of other cells in new onset diabetic NOD miceQ33786819
Developmental control of CD8 T cell-avidity maturation in autoimmune diabetesQ33840423
Islet lymphocyte subsets in male and female NOD mice are qualitatively similar but quantitatively distinct.Q33869101
In situ recognition of autoantigen as an essential gatekeeper in autoimmune CD8+ T cell inflammationQ33927309
Foxp3+ CD25- CD4 T cells constitute a reservoir of committed regulatory cells that regain CD25 expression upon homeostatic expansionQ33932451
Effector and naturally occurring regulatory T cells display no abnormalities in activation induced cell death in NOD miceQ33955180
Homeostatic expansion of T cells during immune insufficiency generates autoimmunity.Q33977505
Tumor necrosis factor-alpha regulation of CD4+CD25+ T cell levels in NOD miceQ34155881
CD4+CD25+ regulatory T cells limit the risk of autoimmune disease arising from T cell receptor crossreactivityQ34161141
The nonobese diabetic mouse as a model of autoimmune diabetes: immune dysregulation gets the NOD.Q34452348
Preventative role of interleukin-17 producing regulatory T helper type 17 (Treg 17) cells in type 1 diabetes in non-obese diabetic mice.Q34488588
Molecular underpinnings of Th17 immune-regulation and their implications in autoimmune diabetesQ38289295
Entry of diabetogenic T cells into islets induces changes that lead to amplification of the cellular responseQ34533933
Cellular and molecular events in the localization of diabetogenic T cells to islets of LangerhansQ34534117
In vivo instruction of suppressor commitment in naive T cellsQ34548023
Defective suppressor function in CD4(+)CD25(+) T-cells from patients with type 1 diabetes.Q34553677
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 diseaseQ34693075
Diversity of regulatory CD4+T cells controlling distinct organ-specific autoimmune diseasesQ34791870
IL-21 signaling is critical for the development of type I diabetes in the NOD mouseQ34823699
T-cell activation: a multidimensional signaling network.Q34858190
Analysis of islet inflammation in human type 1 diabetes.Q34917032
Autoreactive cytotoxic T lymphocytes acquire higher expression of cytotoxic effector markers in the islets of NOD mice after priming in pancreatic lymph nodesQ35070682
The role of T-cells in the pathogenesis of Type 1 diabetes: from cause to cureQ35103993
Beta cell MHC class I is a late requirement for diabetesQ35143964
In vivo dynamics of antigen-specific regulatory T cells not predicted from behavior in vitroQ35171080
Follicular helper T cell signature in type 1 diabetesQ35242659
Role of cytokines in the pathogenesis of autoimmune diabetes mellitusQ35539029
A single autoimmune T cell receptor recognizes more than a million different peptidesQ35668865
Central and peripheral autoantigen presentation in immune toleranceQ35694446
Integrins and T cell-mediated immunityQ35698435
β-cell-specific CD8 T cell phenotype in type 1 diabetes reflects chronic autoantigen exposureQ36019335
Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-beta dependent but does not confer a regulatory phenotypeQ36059631
The NOD mouse: a model of immune dysregulationQ36072434
A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3.Q36078042
Enhanced thymic selection of FoxP3+ regulatory T cells in the NOD mouse model of autoimmune diabetesQ36156876
T cell-mediated inhibition of the transfer of autoimmune diabetes in NOD miceQ36356330
Initiation of autoimmune diabetes by developmentally regulated presentation of islet cell antigens in the pancreatic lymph nodesQ36367942
T cell regulation as a side effect of homeostasis and competitionQ36370619
Pancreatic lymph nodes are required for priming of beta cell reactive T cells in NOD miceQ36370868
Antigen-dependent proliferation of CD4+ CD25+ regulatory T cells in vivoQ36371283
Continuous activation of autoreactive CD4+ CD25+ regulatory T cells in the steady state.Q36371658
The Strength of Persistent Antigenic Stimulation Modulates Adaptive Tolerance in Peripheral CD4+ T CellsQ36371739
Conversion of CD4+ CD25- cells into CD4+ CD25+ regulatory T cells in vivo requires B7 costimulation, but not the thymusQ36402576
Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralizationQ36402763
Sequential development of interleukin 2-dependent effector and regulatory T cells in response to endogenous systemic antigenQ36403106
Single cell analysis shows decreasing FoxP3 and TGFbeta1 coexpressing CD4+CD25+ regulatory T cells during autoimmune diabetesQ36403481
Antigen-specific FoxP3-transduced T-cells can control established type 1 diabetesQ38333256
CD4 T cell differentiation in type 1 diabetes.Q38535279
Mechanisms of diabetic autoimmunity: II--Is diabetes a central or peripheral disorder of effector and regulatory cells?Q38611317
Mechanisms of diabetic autoimmunity: I--the inductive interface between islets and the immune system at onset of inflammationQ38660197
Cell-mediated immunity in type I (insulin-dependent) diabetes of man and the BB rat.Q39844178
Low-affinity major histocompatibility complex-binding peptides in type 1 diabetes.Q39938664
Disordered cellular immunity in type 1 diabetes of man and the BB ratQ40115856
Prevention of diabetes by manipulation of anti-IGRP autoimmunity: high efficiency of a low-affinity peptideQ40418904
Th1 and Th2 cells in autoimmunityQ40442396
Genetic control of autoimmune diabetes in the NOD mouseQ40444847
Different diabetogenic potential of autoaggressive CD8+ clones associated with IFN-gamma-inducible protein 10 (CXC chemokine ligand 10) production but not cytokine expression, cytolytic activity, or homing characteristics.Q40455088
Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases.Q40606547
Ly6C induces clustering of LFA-1 (CD11a/CD18) and is involved in subtype-specific adhesion of CD8 T cellsQ40675952
Autoimmune diabetes results from genetic defects manifest by antigen presenting cellsQ40845491
The effector T cells of diabetic subjects are resistant to regulation via CD4+ FOXP3+ regulatory T cellsQ41146074
Autoimmune diabetes: the role of the islets of LangerhansQ41203054
Pathogenic T cells have a paradoxical protective effect in murine autoimmune diabetes by boosting Tregs.Q41446869
Immune deviation towards Th2 inhibits Th-1-mediated autoimmune diabetesQ41505445
Th1-Th2: reliable paradigm or dangerous dogma?Q41574419
Multiple TCR V beta usage by infiltrates of young NOD mouse islets of Langerhans. A polymerase chain reaction analysisQ41637771
Destabilization of peptide:MHC interaction induces IL-2 resistant anergy in diabetogenic T cellsQ41772561
Interleukin-21 receptor-mediated signals control autoreactive T cell infiltration in pancreatic isletsQ41887106
Complete but curtailed T-cell response to very low-affinity antigenQ41902378
T helper 2 (Th2) T cells induce acute pancreatitis and diabetes in immune-compromised nonobese diabetic (NOD) miceQ41911811
Impaired negative regulation of homeostatically proliferating T cellsQ42015089
Regulatory and effector T cell activation levels are prime determinants of in vivo immune regulationQ42499199
The initial phase of an immune response functions to activate regulatory T cellsQ42571413
Autoreactive diabetogenic T-cells in NOD mice can efficiently expand from a greatly reduced precursor poolQ42657755
Reversal of autoimmunity by boosting memory-like autoregulatory T cellsQ43104323
The effect of regulatory T-cell depletion on the spectrum of organ-specific autoimmune diseases in nonobese diabetic mice at different agesQ43535267
IL-2-targeted therapy ameliorates the severity of graft-versus-host disease: ex vivo selective depletion of host-reactive T cells and in vivo therapyQ43577835
In situ beta cell death promotes priming of diabetogenic CD8 T lymphocytesQ43860764
Release from regulatory T cell-mediated suppression during the onset of tissue-specific autoimmunity is associated with elevated IL-21.Q44051470
CD8(+) T cells specific for beta cells encounter their cognate antigens in the islets of NOD mice.Q44132086
TNF‐α impairs peripheral tolerance towards β‐cells, and local costimulation by B7.1 enhances the effector function of diabetogenic T cellsQ44429966
Killer Treg cells ameliorate inflammatory insulitis in non-obese diabetic mice through local and systemic immunomodulationQ44657813
Pancreatic islet cell phenotype and endocrine function throughout diabetes development in non-obese diabetic miceQ44933149
IL-21 inhibits T cell IL-2 production and impairs Treg homeostasis.Q45951121
The frequency of high avidity T cells determines the hierarchy of determinant spreadingQ46180161
Regulatory T cells prevent transfer of type 1 diabetes in NOD mice only when their antigen is present in vivoQ46359158
Functional and molecular comparison of anergic and regulatory T lymphocytesQ46385458
Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetesQ46512140
Modulation of the TCR stimulation strength can render human activated CD4+ T cells suppressiveQ46920013
Leukocyte attraction through the CCR5 receptor controls progress from insulitis to diabetes in non-obese diabetic mice.Q47214393
TGF-beta-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetesQ47667692
Natural and induced CD4+CD25+ cells educate CD4+CD25- cells to develop suppressive activity: the role of IL-2, TGF-beta, and IL-10.Q47726082
beta cell-specific CD4+ T cell clonotypes in peripheral blood and the pancreatic islets are distinctQ48831166
Surge in regulatory T cells does not prevent onset of hyperglycemia in NOD mice: immune profiles do not correlate with disease severity.Q51177622
Decreased frequencies of CD4+CD25+Foxp3+ cells and the potent CD103+ subset in peripheral lymph nodes correlate with autoimmune disease predisposition in some strains of mice.Q51460050
Spontaneous and homeostatic proliferation of CD4 T cells are regulated by different mechanisms.Q51474938
Naive regulatory T cells: a novel subpopulation defined by resistance toward CD95L-mediated cell death.Q51980708
Cutting edge: homeostatic proliferation of peripheral T lymphocytes is regulated by clonal competition.Q52008546
Immune regulation in type 1 diabetes.Q52048662
A sudden decline in active membrane-bound TGF-beta impairs both T regulatory cell function and protection against autoimmune diabetes.Q52064429
CD25 is a marker for CD4+ thymocytes that prevent autoimmune diabetes in rats, but peripheral T cells with this function are found in both CD25+ and CD25- subpopulations.Q52165458
Peripheral T cell expansion in lymphopenic mice results in a restricted T cell repertoire.Q52926771
Dendritic cells induce autoimmune diabetes and maintain disease via de novo formation of local lymphoid tissueQ36404280
The control of CD4+CD25+Foxp3+ regulatory T cell survivalQ36501531
A mini meta-analysis of studies on CD4+CD25+ T cells in human type 1 diabetes: report of the Immunology of Diabetes Society T Cell Workshop.Q36666034
Insulin-specific T cells are a predominant component of islet infiltrates in pre-diabetic NOD miceQ36736666
Pancreatic islets under attack: cellular and molecular effectorsQ36754684
Disruption of the homeostatic balance between autoaggressive (CD4+CD40+) and regulatory (CD4+CD25+FoxP3+) T cells promotes diabetesQ36803833
T-cell promiscuity in autoimmune diabetesQ36807589
The vicious cycle of apoptotic beta-cell death in type 1 diabetesQ36885374
Construction of self-recognizing regulatory T cells from conventional T cells by controlling CTLA-4 and IL-2 expressionQ36915438
Animal models of spontaneous autoimmune disease: type 1 diabetes in the nonobese diabetic mouseQ36944568
Tissue- and age-specific changes in gene expression during disease induction and progression in NOD miceQ36992100
Autoimmunity since the 1957 clonal selection theory: a little acorn to a large oak.Q37015268
The defect in T-cell regulation in NOD mice is an effect on the T-cell effectorsQ37018786
Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticityQ37100901
Interleukin-21 is required for the development of type 1 diabetes in NOD miceQ37163453
T cell populations in the pancreatic lymph node naturally and consistently expand and contract in NOD mice as disease progressesQ37174434
Inhibition of Th17 cells regulates autoimmune diabetes in NOD mice.Q37193763
Autoimmune mechanisms in type 1 diabetesQ37215820
Apoptosis as a mechanism of T-regulatory cell homeostasis and suppressionQ37270469
Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivoQ37312884
Feedback control of regulatory T cell homeostasis by dendritic cells in vivoQ37331528
Th17 cells promote pancreatic inflammation but only induce diabetes efficiently in lymphopenic hosts after conversion into Th1 cells.Q37370178
Regulation of immunity at tissue sites of inflammationQ37382233
T cell islet accumulation in type 1 diabetes is a tightly regulated, cell-autonomous eventQ37389695
Validity and reproducibility of measurement of islet autoreactivity by T-cell assays in subjects with early type 1 diabetes.Q37400735
Islet-specific T-cell clones from nonobese diabetic mice express heterogeneous T-cell receptors.Q37548447
Checkpoints in the progression of autoimmune disease: lessons from diabetes modelsQ37689425
Cutting edge: type 1 diabetes occurs despite robust anergy among endogenous insulin-specific CD4 T cells in NOD miceQ37704508
Mouse models for the study of autoimmune type 1 diabetes: a NOD to similarities and differences to human diseaseQ37737987
Immune cell crosstalk in type 1 diabetesQ37767586
Does lymphopenia preclude restoration of immune homeostasis? The particular case of type 1 diabetesQ37772010
Pancreatic islet autoimmunityQ38062696
Is autoimmune diabetes caused by aberrant immune activity or defective suppression of physiological self-reactivity?Q38070630
Lymphopenia is detrimental to therapeutic approaches to type 1 diabetes using regulatory T cellsQ38174036
Foxp3-mediated suppression of CD95L expression confers resistance to activation-induced cell death in regulatory T cells.Q53234089
Targeting of IL-2 receptor with a caspase fusion protein disrupts autoimmunity in prediabetic and diabetic NOD mice.Q53357495
Functional waning of naturally occurring CD4+ regulatory T-cells contributes to the onset of autoimmune diabetes.Q53522597
Diabetes in non-obese diabetic mice is not associated with quantitative changes in CD4+ CD25+ Foxp3+ regulatory T cells.Q53560161
In contrast to effector T cells, CD4+CD25+FoxP3+ regulatory T cells are highly susceptible to CD95 ligand- but not to TCR-mediated cell death.Q53669552
CD4+CD25+ regulatory T cells control the progression from periinsulitis to destructive insulitis in murine autoimmune diabetes.Q53846131
Early autoimmune destruction of islet grafts is associated with a restricted repertoire of IGRP-specific CD8+ T cells in diabetic nonobese diabetic mice.Q53855687
Autoimmune diabetes onset results from qualitative rather than quantitative age-dependent changes in pathogenic T-cells.Q53859655
Cross-priming of diabetogenic T cells dissociated from CTL-induced shedding of beta cell autoantigens.Q53909275
Deficient activation and resistance to activation-induced apoptosis of CD8+ T cells is associated with defective peripheral tolerance in nonobese diabetic mice.Q53929277
Defect in activation-induced cell death in non-obese diabetic (NOD) T lymphocytes.Q53929870
Th1 to Th2 cytokine shifts in nonobese diabetic mice: sometimes an outcome, rather than the cause, of diabetes resistance elicited by immunostimulation.Q54024223
B lymphocytes are critical antigen-presenting cells for the initiation of T cell-mediated autoimmune diabetes in nonobese diabetic mice.Q54120741
Deficiency in NOD antigen-presenting cell function may be responsible for suboptimal CD4+CD25+ T-cell-mediated regulation and type 1 diabetes development in NOD mice.Q54594961
Few differences in cytokines between patients newly diagnosed with type 1 diabetes and their healthy siblingsQ58201144
Transient expression of FOXP3 in human activated nonregulatory CD4+ T cellsQ58234949
Progression of autoimmune diabetes driven by avidity maturation of a T-cell populationQ58328335
Increased thymic development of regulatory T cells in NOD mice is functionally dissociated from type I diabetes susceptibilityQ61727549
Defective expression of the apoptosis-inducing CD95 (Fas/APO-1) molecule on T and B cells in IDDMQ63256810
IL-21 Counteracts the Regulatory T Cell-Mediated Suppression of Human CD4+ T LymphocytesQ63325580
Expression of Ly-6C by T lymphocytes of NOD mice after CD3-complex stimulation. Identification of activated cells during insulitis of prediabetic miceQ68463912
Following a diabetogenic T cell from genesis through pathogenesisQ70488192
Demonstration of a TH1 cytokine profile in the late phase of NOD insulitisQ71145935
The diabetic BB rat. Neither Th1 nor Th2?Q71542134
Activation of CD8+ T lymphocytes in insulin-dependent diabetes mellitusQ73162675
Characterization of peripheral regulatory CD4+ T cells that prevent diabetes onset in nonobese diabetic miceQ73289663
Human anergic/suppressive CD4(+)CD25(+) T cells: a highly differentiated and apoptosis-prone populationQ73740429
Naturally anergic and suppressive CD25(+)CD4(+) T cells as a functionally and phenotypically distinct immunoregulatory T cell subpopulationQ74080415
Adaptive tolerance of CD4+ T cells in vivo: multiple thresholds in response to a constant level of antigen presentationQ74321454
Independent genetic regulation of T-cell and antigen-presenting cell participation in autoimmune islet inflammationQ74371129
Modulation of Fas-dependent apoptosis: a dynamic process controlling both the persistence and death of CD4 regulatory T cells and effector T cellsQ74410084
Cellular and molecular mechanisms for the initiation and progression of beta cell destruction resulting from the collaboration between macrophages and T cellsQ74534976
A defect in central tolerance in NOD miceQ74825850
Mature mainstream TCR alpha beta+CD4+ thymocytes expressing L-selectin mediate "active tolerance" in the nonobese diabetic mouseQ77186394
Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivoQ77342616
Epitope dominance: evidence for reciprocal determinant spreading to glutamic acid decarboxylase in non-obese diabetic miceQ77488356
Pancreatic lymph node-derived CD4(+)CD25(+) Treg cells: highly potent regulators of diabetes that require TRANCE-RANK signalsQ77704341
T-cell compartments of prediabetic NOD miceQ78830234
Dynamics of pathogenic and suppressor T cells in autoimmune diabetes developmentQ79125427
Diabetogenic T cells are primed both in pancreatic and gut-associated lymph nodes in NOD miceQ79318828
Identical beta cell-specific CD8(+) T cell clonotypes typically reside in both peripheral blood lymphocyte and pancreatic isletsQ79609646
CD4+ CD25+ [corrected] regulatory T cells render naive CD4+ CD25- T cells anergic and suppressiveQ79629254
Indexation as a novel mechanism of lymphocyte homeostasis: the number of CD4+CD25+ regulatory T cells is indexed to the number of IL-2-producing cellsQ79754976
No alterations in the frequency of FOXP3+ regulatory T-cells in type 1 diabetesQ79843142
P433issue4
P921main subjectobesityQ12174
P304page(s)377-388
P577publication date2016-01-09
P1433published inImmunologyQ15754984
P1476titleMechanisms of autoimmunity in the non-obese diabetic mouse: effector/regulatory cell equilibrium during peak inflammation
P478volume147