Heparanase prevents the development of type 1 diabetes in non‐obese diabetic mice by regulating T‐cell activation and cytokines production

2008 ◽  
Vol 24 (5) ◽  
pp. 413-421 ◽  
Author(s):  
Menachem Bitan ◽  
Lola Weiss ◽  
Michael Zeira ◽  
Shoshana Reich ◽  
Orit Pappo ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Diabetic Mice

Reduced CD4+T cell activation in children with type 1 diabetes carrying the PTPN22/Lyp 620Trp variant

2008 ◽  
Vol 31 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Johanna Aarnisalo ◽  
Andras Treszl ◽  
Peter Svec ◽  
Jane Marttila ◽  
Viveka Öling ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd4 T Cell

scholarly journals Sphingosine-1-Phosphate Reduces CD4+ T-Cell Activation in Type 1 Diabetes Through Regulation of Hypoxia-Inducible Factor Short Isoform I.1 and CD69

Diabetes ◽  
2007 ◽  
Vol 57 (2) ◽  
pp. 484-493 ◽  
Author(s):  
S. Srinivasan ◽  
D. T. Bolick ◽  
D. Lukashev ◽  
C. Lappas ◽  
M. Sitkovsky ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Hypoxia Inducible Factor ◽  
Cd4 T Cell ◽  
Sphingosine 1 Phosphate

scholarly journals CD226 Deletion Reduces Type 1 Diabetes in the NOD Mouse by Impairing Thymocyte Development and Peripheral T Cell Activation

2020 ◽  
Vol 11 ◽  
Author(s):  
Melanie R. Shapiro ◽  
Wen-I Yeh ◽  
Joshua R. Longfield ◽  
John Gallagher ◽  
Caridad M. Infante ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Nod Mouse ◽  
Thymocyte Development

scholarly journals CD5 expressing CD8+ T cell subsets differ between children with Type 1 Diabetes and controls

2021 ◽  
Author(s):  
Josefine Wadenpohl ◽  
Julia Seyfarth ◽  
Paul Hehenkamp ◽  
Maximilian Hoffmann ◽  
Sebastian Kummer ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
B Cell ◽  
Quantitative Pcr ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell

Different lymphocyte subsets are involved in autoimmune pathogenesis of Type 1 Diabetes (T1D). Previous studies suggested a role of CD5 expressing T and B cells including rare unconventional lymphocytes with combined T- and B-cell features (DE cells). We performed algorithm-supported multi-parameter flow cytometry and quantitative PCR to investigate immune cell subsets and DE cells in children with T1D (n=20) and matched controls (n=20). Comparisons of conventional immune cells detected increased proportions of CD3+ T cells in T1D patients whereas CD19+ B cell proportions were comparable to controls. Self-organizing maps for flow cytometry analyses (FlowSOM) showed highly similar CD5 expressing B-cell subsets and no differences for DE cells were detected between the study groups by flow cytometry or specific quantitative PCR. Notably, differences in CD8 positive T cells were indicated by FlowSOM and similarity-based tSNE analyses. Study group comparison confirmed significantly reduced CD8+ T-cell proportions with moderate or low CD5 expression in T1D patients. Finally, In vitro experiments showed stable CD5 expression differences of CD8+ T cells after T-cell activation, cytokine stimulation and culture. We observed differences of T-cell co-receptor CD5 expression in T1D patients with potential relevance for immune regulation of CD8+ T-cell activation.

scholarly journals Caspase-3-Dependent β-Cell Apoptosis in the Initiation of Autoimmune Diabetes Mellitus

2005 ◽  
Vol 25 (9) ◽  
pp. 3620-3629 ◽  
Author(s):  
Nicole Liadis ◽  
Kiichi Murakami ◽  
Mohamed Eweida ◽  
Alisha R. Elford ◽  
Laura Sheu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Apoptosis ◽  
Cell Activation ◽  
Caspase 3 ◽  
Autoimmune Diabetes ◽  
Β Cell

ABSTRACT β-Cell apoptosis is a key event contributing to the pathogenesis of type 1 diabetes mellitus. In addition to apoptosis being the main mechanism by which β cells are destroyed, β-cell apoptosis has been implicated in the initiation of type 1 diabetes mellitus through antigen cross-presentation mechanisms that lead to β-cell-specific T-cell activation. Caspase-3 is the major effector caspase involved in apoptotic pathways. Despite evidence supporting the importance of β-cell apoptosis in the pathogenesis of type 1 diabetes, the specific role of caspase-3 in this process is unknown. Here, we show that Caspase-3 knockout (Casp3 − /−) mice were protected from developing diabetes in a multiple-low-dose streptozotocin autoimmune diabetes model. Lymphocyte infiltration of the pancreatic islets was completely absent in Casp3 − /− mice. To determine the role of caspase-3-dependent apoptosis in disease initiation, a defined antigen-T-cell receptor transgenic system, RIP-GP/P14 double-transgenic mice with Casp3 null mutation, was examined. β-cell antigen-specific T-cell activation and proliferation were observed only in the pancreatic draining lymph node of RIP-GP/P14/Casp3 + /− mice, but not in mice lacking caspase-3. Together, our findings demonstrate that caspase-3-mediated β-cell apoptosis is a requisite step for T-cell priming, a key initiating event in type 1 diabetes.

scholarly journals βig-h3 Represses T-Cell Activation in Type 1 Diabetes

Diabetes ◽  
2015 ◽  
Vol 64 (12) ◽  
pp. 4212-4219 ◽  
Author(s):  
Maeva Patry ◽  
Romain Teinturier ◽  
Delphine Goehrig ◽  
Cornelia Zetu ◽  
Doriane Ripoche ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation

scholarly journals T Cell Activation by Coxsackievirus B4 Antigens in Type 1 Diabetes Mellitus: Evidence for Selective TCR Vβ Usage Without Superantigenic Activity

2001 ◽  
Vol 167 (6) ◽  
pp. 3513-3520 ◽  
Author(s):  
Ruben Varela-Calvino ◽  
Gianluca Sgarbi ◽  
Lucy R. Wedderburn ◽  
Colin M. Dayan ◽  
Jenny Tremble ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Type 1 Diabetes Mellitus ◽  
T Cell Activation ◽  
Cell Activation ◽  
Coxsackievirus B4

scholarly journals NLRP3 deficiency protects from type 1 diabetes through the regulation of chemotaxis into the pancreatic islets

2015 ◽  
Vol 112 (36) ◽  
pp. 11318-11323 ◽  
Author(s):  
Changyun Hu ◽  
Heyuan Ding ◽  
Yangyang Li ◽  
James A. Pearson ◽  
Xiaojun Zhang ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Pancreatic Islet ◽  
T Cell Activation ◽  
Chemokine Receptors ◽  
Cell Activation ◽  
Islet Cells ◽  
Human Subjects ◽  
Dependent Manner

Studies in animal models and human subjects have shown that both innate and adaptive immunity contribute to the pathogenesis of type 1 diabetes (T1D). Whereas the role of TLR signaling pathways in T1D has been extensively studied, the contribution of the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein (NLRP) 3 inflammasome pathway remains to be explored. In this study, we report that NLRP3 plays an important role in the development of T1D in the nonobese diabetic (NOD) mouse model. NLRP3 deficiency not only affected T-cell activation and Th1 differentiation, but also modulated pathogenic T-cell migration to the pancreatic islet. The presence of NLRP3 is critical for the expression of the chemokine receptors CCR5 and CXCR3 on T cells. More importantly, NLRP3 ablation reduced the expression of chemokine genes CCL5 and CXCL10 on pancreatic islet cells in an IRF-1–dependent manner. Our results suggest that molecules involved in chemotaxis, accompanied by the activation of the NLRP3 inflammasome, may be effective targets for the treatment of T1D.

scholarly journals A Conserved Calcineurin-binding Motif in Human T Lymphotropic Virus Type 1 p12IFunctions to Modulate Nuclear Factor of Activated T Cell Activation

2003 ◽  
Vol 278 (18) ◽  
pp. 15550-15557 ◽  
Author(s):  
Seung-jae Kim ◽  
Wei Ding ◽  
Björn Albrecht ◽  
Patrick L. Green ◽  
Michael D. Lairmore
Keyword(s):  
T Cell ◽  
Virus Type ◽  
T Cell Activation ◽  
Cell Activation ◽  
Binding Motif ◽  
Nuclear Factor ◽  
T Lymphotropic Virus ◽  
Activated T Cell
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