ArticleJournal of leukocyte biology2008
Disruption of the homeostatic balance between autoaggressive (CD4+CD40+) and regulatory (CD4+CD25+FoxP3+) T cells promotes diabetes.
Article in Journal of leukocyte biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- The CD40-CD154 axis in transplantation: from immunobiology to therapeutic targeting.Frontiers in immunology · 2026Review
- A CD40-targeting peptide, OPT501, modulates inflammation in canine diabetes mellitus improving clinical outcomes.Frontiers in immunology · 2026Article
- Higher CD4Scientific reports · 2023Article
- Ocrevus reduces TH40 cells, a biomarker of systemic inflammation, in relapsing multiple sclerosis (RMS) and in progressive multiple sclerosis (PMS).Journal of neuroimmunology · 2023Article
- Two to Tango: Dialogue between Adaptive and Innate Immunity in Type 1 Diabetes.Journal of diabetes research · 2020Review
- CD40-mediated signalling influences trafficking, T-cell receptor expression, and T-cell pathogenesis, in the NOD model of type 1 diabetes.Immunology · 2017Article
- Th40 cells (CD4+CD40+ Tcells) drive a more severe form of Experimental Autoimmune Encephalomyelitis than conventional CD4 T cells.PloS one · 2017Article
- Overlooked Mechanisms in Type 1 Diabetes Etiology: How Unique Costimulatory Molecules Contribute to Diabetogenesis.Frontiers in endocrinology · 2017Review
- Of the multiple mechanisms leading to type 1 diabetes, T cell receptor revision may play a prominent role (is type 1 diabetes more than a single disease?).Clinical and experimental immunology · 2016Review
- Age-dependent divergent effects of OX40L treatment on the development of diabetes in NOD mice.Autoimmunity · 2016Article
- Mechanisms of autoimmunity in the non-obese diabetic mouse: effector/regulatory cell equilibrium during peak inflammation.Immunology · 2016Review
- Insulin-like growth factor-1 stimulates regulatory T cells and suppresses autoimmune disease.EMBO molecular medicine · 2014Article
- A CD40-targeted peptide controls and reverses type 1 diabetes in NOD mice.Diabetologia · 2014Article
- Pro-inflammatory T-lymphocytes rapidly infiltrate into the brain and contribute to neuronal injury following cardiac arrest and cardiopulmonary resuscitation.Journal of neuroimmunology · 2014Article
- Defining a new biomarker for the autoimmune component of Multiple Sclerosis: Th40 cells.Journal of neuroimmunology · 2014Article
- CD40 interacts directly with RAG1 and RAG2 in autoaggressive T cells and Fas prevents CD40-induced RAG expression.Cellular & molecular immunology · 2013Article
- Elimination of T cell reactivity to pancreatic β cells and partial preservation of β cell activity by peptide blockade of LFA-1:ICAM-1 interaction in the NOD mouse model.Clinical immunology (Orlando, Fla.) · 2013Article
- An alternative role for Foxp3 as an effector T cell regulator controlled through CD40.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Article
- Effector and naturally occurring regulatory T cells display no abnormalities in activation induced cell death in NOD mice.PloS one · 2011Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Although regulatory T cells (Tregs) are well described, identifying autoaggressive effector T cells has proven more difficult. However, we identified CD4loCD40+ (Th40) cells as being necessary and sufficient for diabetes in the NOD mouse model. Importantly, these cells are present in pancreata of prediabetic and diabetic NOD mice, and Th40 cells but not CD4+CD40(-) T cells transfer progressive insulitis and diabetes to NOD.scid recipients. Nonobese-resistant (NOR) mice have the identical T cell developmental background as NOD mice, yet they are diabetes-resistant. The seminal issue is how NOR mice remain tolerant to diabetogenic self-antigens. We show here that autoaggressive T cells develop in NOR mice and are confined to the Th40 subset. However, NOR mice maintain Treg numbers equivalent to their Th40 numbers. NOD mice have statistically equal numbers of CD4+CD25+forkhead box P3+intrinsic Tregs compared with NOR or nonautoimmune BALB/c mice, and NOD Tregs are equally as suppressive as NOR Tregs. A critical difference is that NOD mice develop expanded numbers of Th40 cells. We suggest that a determinant factor for autoimmunity includes the Th40:Treg ratio. Mechanistically, NOD Th40 cells have low susceptibility to Fas-induced cell death and unlike cells from NOR and BALB/c mice, have predominantly low Fas expression. CD40 engagement of Th40 cells induces Fas expression but further confers resistance to Fas-mediated cell death in NOD mice. A second fundamental difference is that NOD Th40 cells undergo much more rapid homeostatic expansion than Th40 cells from NOR mice.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.