Autoantigen-specific memory CD4+ T cells are prevalent early in progression to Type 1 diabetes

Öling, Viveka; Reijonen, Helena; Simell, Olli; Knip, Mikael; Ilonen, Jorma

doi:10.1016/j.cellimm.2011.12.008

Cited by 35 publications

(19 citation statements)

References 37 publications

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“…Of note, HLA-A2 is found also in about 50% of the general European-descent population; the often-reported detection of circulating autoreactive T cells in healthy individuals (102) may derive from negative selection processes that are inherently imperfect for islet cell selfmolecules. However, autoreactive T cells in T1D patients are reportedly enriched in memory cells versus a naive phenotype in healthy subjects (103,104). The positive effects of treatment with an anti-memory cell agent in patients with recently diagnosed T1D supports the importance of memory autoreactive T cells in this disease (105,106).…”

Section: T Cells In the Prediabetic Pancreasmentioning

confidence: 92%

Autoreactive T cells in type 1 diabetes

Pugliese¹

2017

Journal of Clinical Investigation

269

226

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Section: T Cells In the Prediabetic Pancreasmentioning

confidence: 92%

Autoreactive T cells in type 1 diabetes

Pugliese¹

2017

Journal of Clinical Investigation

269

226

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“…Although GAD65 levels in murine pancreatic beta cells are very low, it is a major autoantigen in the pathogenesis of T1D in the NOD mouse [204]. GAD65-specific T cells have been demonstrated in both T1D patients and the NOD mouse [205–209]. Adoptive transfer of GAD65-reactive T cells isolated from NOD mice caused recipient animals to develop T1D [207, 210], supporting the concept of diabetogenic GAD65-specific T cells in the pathogenesis of T1D.…”

Section: B-cell Tolerancementioning

confidence: 99%

B Cells in Autoimmune Diseases

2012

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The role of B cells in autoimmune diseases involves different cellular functions, including the well-established secretion of autoantibodies, autoantigen presentation and ensuing reciprocal interactions with T cells, secretion of inflammatory cytokines, and the generation of ectopic germinal centers. Through these mechanisms B cells are involved both in autoimmune diseases that are traditionally viewed as antibody mediated and also in autoimmune diseases that are commonly classified as T cell mediated. This new understanding of the role of B cells opened up novel therapeutic options for the treatment of autoimmune diseases. This paper includes an overview of the different functions of B cells in autoimmunity; the involvement of B cells in systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes; and current B-cell-based therapeutic treatments. We conclude with a discussion of novel therapies aimed at the selective targeting of pathogenic B cells.

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“…In T1D mice, islet-infiltrating cells were characterized as CD44 High CD62L Low which appeared to be memory cells and able to transfer insulitis and diabetes [6]. Using MHC class II tetramers, autoantigen-specific CD4 Tm cells are prevalent in the early progression to T1D [7]. In this study, CD44 High CD62L Low cells were used as markers of effector Tm cells in T1D mice.…”

Section: Introductionmentioning

confidence: 97%

Tolerogenic Vaccination Reduced Effector Memory CD4 T Cells and Induced Effector Memory Treg Cells for Type I Diabetes Treatment

et al. 2013

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BackgroundVaccination could induce immune tolerance and protected NOD mice from the development of type I diabetes (T1D). We previously demonstrated that insulin peptide (B9-23) combined with dexamethasone (DEX) stimulated the expansion of antigen specific regulatory T (Treg) cells which in turn effectively prevented T1D in NOD mice. Here, we aimed to investigate the therapeutic effect of tolerogenic vaccination for T1D treatment.Methodology/Principal FindingsThe diabetic NOD mice (Blood glucose level ≧250 mg/dl) were treated with B9-23 and DEX twice. The tolerance was restored by blocking maturation of dendritic cells (DCs) and inducing Treg cells in treated NOD mice. Remarkably, the reduction of autoreactive effector memory CD4 T (Tm) cells and the induction of functional effector memory Treg (mTreg) cells contributed to the improvement of T1D in treated NOD mice.Conclusions/SignificanceTolerogenic vaccination restored tolerance and ameliorated T1D by suppressing effector CD4 Tm cells and inducing effector mTreg cells. Our findings implicate the potential of tolerogenic vaccination for T1D treatment.

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Autoantigen-specific memory CD4+ T cells are prevalent early in progression to Type 1 diabetes

Cited by 35 publications

References 37 publications

Autoreactive T cells in type 1 diabetes

Autoreactive T cells in type 1 diabetes

B Cells in Autoimmune Diseases

Tolerogenic Vaccination Reduced Effector Memory CD4 T Cells and Induced Effector Memory Treg Cells for Type I Diabetes Treatment

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