scholarly journals Development of Type 1 Diabetes Mellitus in Nonobese Diabetic Mice Follows Changes in Thymocyte and Peripheral T Lymphocyte Transcriptional Activity

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Thais A. Fornari ◽  
Paula B. Donate ◽  
Claudia Macedo ◽  
Elza T. Sakamoto-Hojo ◽  
Eduardo A. Donadi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Activation ◽  
Transcriptional Activity ◽  
Cell Activation ◽  
Autoimmune Diabetes ◽  
Immune Reactivity ◽  
Diabetic Mice ◽  
Nonobese Diabetic

As early as one month of age, nonobese diabetic (NOD) mice feature pancreatic infiltration of autoreactive T lymphocytes, which destruct insulin-producing beta cells, producing autoimmune diabetes mellitus (T1D) within eight months. Thus, we hypothesized that during the development of T1D, the transcriptional modulation of immune reactivity genes may occur as thymocytes mature into peripheral T lymphocytes. The transcriptome of thymocytes and peripheral CD3+T lymphocytes from prediabetic or diabetic mice analyzed through microarray hybridizations identified 2,771 differentially expressed genes. Hierarchical clustering grouped mice according to age/T1D onset and genes according to their transcription profiling. The transcriptional activity of thymocytes developing into peripheral T lymphocytes revealed sequential participation of genes involved with CD4+/CD8+T-cell differentiation (Themis), tolerance induction by Tregs (Foxp3), and apoptosis (Fasl) soon after T-cell activation (IL4), while the emergence of T1D coincided with the expression of cytotoxicity (Crtam) and inflammatory response genes (Tlr) by peripheral T lymphocytes.

scholarly journals Correction: Autoimmunity during Thymectomy-Induced Lymphopenia: Role of Thymus Ablation and Initial Effector T Cell Activation Timing in Nonobese Diabetic Mice

2010 ◽  
Vol 185 (5) ◽  
pp. 3111-3111
Author(s):  
Marie-Claude Gagnerault ◽  
Olivia Lanvin ◽  
Virginie Pasquier ◽  
Corinne Garcia ◽  
Diane Damotte ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Diabetic Mice ◽  
Effector T Cell ◽  
Nonobese Diabetic ◽  
Nonobese Diabetic Mice

scholarly journals Autoimmunity during Thymectomy-Induced Lymphopenia: Role of Thymus Ablation and Initial Effector T Cell Activation Timing in Nonobese Diabetic Mice

2009 ◽  
Vol 183 (8) ◽  
pp. 4913-4920 ◽  
Author(s):  
Marie-Claude Gagnerault ◽  
Olivia Lanvin ◽  
Virginie Pasquier ◽  
Corinne Garcia ◽  
Diane Damotte ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Diabetic Mice ◽  
Effector T Cell ◽  
Nonobese Diabetic ◽  
Nonobese Diabetic Mice

scholarly journals Correction: Levels of Adenosine Deaminase on Dendritic Cells Promote Autoreactive T Cell Activation and Diabetes in Nonobese Diabetic Mice

2011 ◽  
Vol 187 (4) ◽  
pp. 2031-2031
Author(s):  
Faranak Ghaemi Oskouie ◽  
Afshin Shameli ◽  
Ailian Yang ◽  
Melanie D. Desrosiers ◽  
Ashley D. Mucsi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Adenosine Deaminase ◽  
T Cell Activation ◽  
Cell Activation ◽  
Diabetic Mice ◽  
Nonobese Diabetic ◽  
Autoreactive T Cell ◽  
Nonobese Diabetic Mice

scholarly journals Differential Contributions of APC Subsets to T Cell Activation in Nonobese Diabetic Mice

2008 ◽  
Vol 180 (8) ◽  
pp. 5235-5249 ◽  
Author(s):  
Annette M. Marleau ◽  
Kelly L. Summers ◽  
Bhagirath Singh
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Diabetic Mice ◽  
Nonobese Diabetic ◽  
Nonobese Diabetic Mice

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 High Levels of Adenosine Deaminase on Dendritic Cells Promote Autoreactive T Cell Activation and Diabetes in Nonobese Diabetic Mice

2011 ◽  
Vol 186 (12) ◽  
pp. 6798-6806 ◽  
Author(s):  
Faranak Ghaemi Oskouie ◽  
Afshin Shameli ◽  
Ailian Yang ◽  
Melanie D. Desrosiers ◽  
Ashley D. Mucsi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Adenosine Deaminase ◽  
T Cell Activation ◽  
Cell Activation ◽  
Diabetic Mice ◽  
Nonobese Diabetic ◽  
Autoreactive T Cell ◽  
Nonobese Diabetic Mice

scholarly journals Immune function of the blood-brain barrier: incomplete presentation of protein (auto-)antigens by rat brain microvascular endothelium in vitro.

1990 ◽  
Vol 110 (5) ◽  
pp. 1757-1766 ◽  
Author(s):  
W Risau ◽  
B Engelhardt ◽  
H Wekerle
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Rat Brain ◽  
Blood Brain Barrier ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ifn Gamma

The endothelial blood-brain barrier (BBB) has a critical role in controlling lymphocyte traffic into the central nervous system (CNS), both in physiological immunosurveillance, and in its pathological aberrations. The intercellular signals that possibly could induce lymphocytes to cross the BBB include immunogenic presentation of protein (auto-)antigens by BBB endothelia to circulating T lymphocytes. This concept has raised much, though controversial, attention. We approached this problem by analyzing in vitro immunospecific interactions between clonal rat T lymphocyte lines with syngeneic, stringently purified endothelial monolayer cultures from adult brain micro-vessels. The rat brain endothelia (RBE) were established from rat brain capillaries using double collagenase digestion, density gradient fractionation and selective cytolysis of contaminating pericytes by anti-Thy 1.1 antibodies and complement. Incubation with interferon-gamma in most of the brain-derived endothelial cells induced Ia-antigens in the cytoplasm and on the cell surface in some of the cells. Before the treatment, the cells were completely Ia-negative. Pericytes were unresponsive to IFN-gamma treatment. When confronted with syngeneic T cell lines specific for protein (auto-)antigens (e.g., ovalbumin and myelin basic protein, MBP), RBE were completely unable to induce antigen-specific proliferation of syngeneic T lymphocytes irrespective of pretreatment with IFN-gamma and of cell density. RBE were inert towards the T cells, and did not suppress T cell activation induced by other "professional" antigen presenting cells (APC) such as thymus-derived dendritic cells or macrophages. IFN-gamma-treated RBE were, however, susceptible to immunospecific T cell killing. They were lysed by MBP-specific T cells in the presence of the specific antigen or Con A. Antigen dependent lysis was restricted by the appropriate (MHC) class II product. We conclude that the interaction of brain endothelial cells with encephalitogenic T lymphocytes may involve recognition of antigen in the molecular context of relevant MHC products, but that this interaction per se is insufficient to initiate the full T cell activation program.

Abstract P347: γδ T Cells Drive CD4 + And CD8 + T Cell Activation In Hypertension

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Antoine Caillon ◽  
Pierre Paradis ◽  
Ernesto L Schiffrin
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Vascular Injury ◽  
T Cell Activation ◽  
Cell Activation ◽  
Γδ T Cells ◽  
Ang Ii ◽  
Adaptive Immune Cells ◽  
Induced Hypertension

Objective: Both innate (monocyte/macrophages) and adaptive immune cells (T lymphocytes) have been shown to play a role in the development of vascular injury in hypertension. Recently, we demonstrated that a small subset of “innate-like” T lymphocytes, expressing the γ/δ T cell receptor (TCR) rather than the αβ TCR, plays a key role in hypertension and vascular injury. We demonstrated an increased number and activation (CD69 + ) of γδ T cells during the development of hypertension caused by angiotensin (Ang) II infusion, and that deficiency in γδ T cells prevented Ang II-induced hypertension, resistance artery endothelial dysfunction and spleen T-cell activation in mice. We hypothesized that γδ T cells mediate activation of other T cells in hypertension. Method and Results: Fourteen to 15-week old male C57BL/6 wild-type (WT) mice were infused with Ang II (490 ng/kg/min, SC) for 3, 7 and 14 days (n=5-7) and spleen T cell profile was determined by flow cytometry. A correlation was demonstrated between the frequency (FREQ) and the number (#) of activated CD69 + γδ T cells and CD4 + CD69 + T cells (FREQ: r=0.41, P <0.05 and #: r=0.58, P <0.001) and CD8 + CD69 + T cells (FREQ: r=0.36, P <0.05 and #: r=0.50, P <0.01). We also demonstrated a high correlation between the # of CD69 + γδ T cells expressing CD27, a marker of interferon-γ expressing cells and a member of the T-T interaction molecules, with CD4 + CD69 + (r=0.88, P <0.001) and CD8 + CD69 + (r=0.81, P <0.01) T cells after 7 days of Ang II infusion. Conclusion: This study demonstrated an association between CD27 + CD69 + γδ T cells and activated T cells. These results suggest that γδ T cells drive activation of other T cells in Ang II-induced hypertension. Targeting γδ T cells may contribute to reduce inflammation in hypertension.

Sign in / Sign up

Export Citation Format

Share Document