Synergy of class I and class II MHC deficiency (C1D and C2D) islets and early short-term suppression in achieving long-term islet graft survival and tolerance induction

1999 ◽  
Vol 31 (1-2) ◽  
pp. 635-636 ◽  
Author(s):  
K Pittman ◽  
P Berzina ◽  
J Contreras ◽  
G Bilbao ◽  
F Thomas ◽  
...  
Author(s):  
T. A. Stewart ◽  
D. Liggitt ◽  
S. Pitts ◽  
L. Martin ◽  
M. Siegel ◽  
...  

Insulin-dependant (Type I) diabetes mellitus (IDDM) is a metabolic disorder resulting from the lack of endogenous insulin secretion. The disease is thought to result from the autoimmune mediated destruction of the insulin producing ß cells within the islets of Langerhans. The disease process is probably triggered by environmental agents, e.g. virus or chemical toxins on a background of genetic susceptibility associated with particular alleles within the major histocompatiblity complex (MHC). The relation between IDDM and the MHC locus has been reinforced by the demonstration of both class I and class II MHC proteins on the surface of ß cells from newly diagnosed patients as well as mounting evidence that IDDM has an autoimmune pathogenesis. In 1984, a series of observations were used to advance a hypothesis, in which it was suggested that aberrant expression of class II MHC molecules, perhaps induced by gamma-interferon (IFN γ) could present self antigens and initiate an autoimmune disease. We have tested some aspects of this model and demonstrated that expression of IFN γ by pancreatic ß cells can initiate an inflammatory destruction of both the islets and pancreas and does lead to IDDM.


2020 ◽  
Vol 8 (3) ◽  
pp. 144-156
Author(s):  
Şule KARATAŞ ◽  
Fatma SAVRAN OĞUZ

Introduction: Peptides obtained by processing intracellular and extracellular antigens are presented to T cells to stimulate the immune response. This presentation is made by peptide receptors called major histocompatibility complex (MHC) molecules. The regulation mechanisms of MHC molecules, which have similar roles in the immune response, especially at the gene level, have significant differences according to their class. Objective: Class I and class II MHC molecules encoded by MHC genes on the short arm of the sixth chromosome are peptide receptors that stimulate T cell response. These peptides, which will enable the recognition of the antigen from which they originate, are loaded into MHC molecules and presented to T cells. Although the principles of loading and delivering peptides are similar for both molecules, the peptide sources and peptide loading mechanisms are different. In addition, class I molecules are expressed in all nucleated cells while class II molecules are expressed only in Antigen Presentation Cells (APC). These differences; It shows that MHC class I is not expressed by exactly the same transcriptional mechanisms as MHC class II. In our article, we aimed to compare the gene expressions of both classes and reveal their similarities and differences. Discussion and Conclusion: A better understanding of the transcriptional mechanisms of MHC molecules will reveal the role of these molecules in diseases more clearly. In our review, we discussed MHC gene regulation mechanisms with presence of existing informations, which is specific to the MHC class, for contribute to future research. Keywords: MHC class I, MHC class II, MHC gene regulation, promoter, SXY module, transcription


1989 ◽  
Vol 26 (12) ◽  
pp. 1095-1104 ◽  
Author(s):  
Teresa Burke ◽  
Karen Pollok ◽  
William Cushley ◽  
E. Charles Snow

2014 ◽  
Vol 7 (1) ◽  
pp. 115-122
Author(s):  
Jodi M. Smith ◽  
Vikas R. Dharnidharka

Significant progress has been made in pediatric kidney transplantation. Advances in immunosuppression have dramatically decreased rates of acute rejection leading to improved short term graft survival but similar improvements in long term graft survival remain elusive. Changes in allocation policy provide the pediatric population with timely access to transplant but there remains concern about the impact of less HLA matching and a decrease in living donors. This report presents data from North America on these successes and the ongoing challenges that face the pediatric transplant community.


2018 ◽  
Vol 88 (5) ◽  
pp. 530-537
Author(s):  
E. Erin Bilbo ◽  
Steven D. Marshall ◽  
Karin A. Southard ◽  
Verrasathpurush Allareddy ◽  
Nathan Holton ◽  
...  

ABSTRACT Objectives: The long-term skeletal effects of Class II treatment in growing individuals using high-pull facebow headgear and fixed edgewise appliances have not been reported. The purpose of this study was to evaluate the long-term skeletal effects of treatment using high-pull headgear followed by fixed orthodontic appliances compared to an untreated control group. Materials and Methods: Changes in anteroposterior and vertical cephalometric measurements of 42 Class II subjects (n = 21, mean age = 10.7 years) before treatment, after headgear correction to Class I molar relationship, after treatment with fixed appliances, and after long-term retention (mean 4.1 years), were compared to similar changes in a matched control group (n = 21, mean age = 10.9 years) by multivariable linear regression models. Results: Compared to control, the study group displayed significant long-term horizontal restriction of A-point (SNA = −1.925°, P < .0001; FH-NA = −3.042°, P < .0001; linear measurement A-point to Vertical Reference = −3.859 mm, P < .0001) and reduction of the ANB angle (−1.767°, P < .0001), with no effect on mandibular horizontal growth or maxillary and mandibular vertical skeletal changes. A-point horizontal restriction and forward mandibular horizontal growth accompanied the study group correction to Class I molar, and these changes were stable long term. Conclusions: One phase treatment for Class II malocclusion with high-pull headgear followed by fixed orthodontic appliances resulted in correction to Class I molar through restriction of horizontal maxillary growth with continued horizontal mandibular growth and vertical skeletal changes unaffected. The anteroposterior molar correction and skeletal effects of this treatment were stable long term.


2022 ◽  
Author(s):  
Braxton L. Jamison ◽  
James E. DiLisio ◽  
K. Scott Beard ◽  
Tobias Neef ◽  
Brenda Bradley ◽  
...  

The induction of antigen (Ag)-specific tolerance and replacement of islet β-cells are major ongoing goals for the treatment of Type 1 Diabetes (T1D). Our group previously showed that a hybrid insulin peptide (2.5HIP) is a critical autoantigen for diabetogenic CD4<sup>+</sup> T cells in the non-obese diabetic (NOD) mouse model. In this study, we investigated whether induction of Ag-specific tolerance using 2.5HIP-coupled tolerogenic nanoparticles (NPs) could protect diabetic NOD mice from disease recurrence upon syngeneic islet transplantation. Islet graft survival was significantly prolonged in mice treated with 2.5HIP NPs, but not NPs containing the insulin B chain peptide 9-23. Protection in 2.5HIP NP-treated mice was attributed both to the simultaneous induction of anergy in 2.5HIP-specific effector T cells and to the expansion of Foxp3+ regulatory T cells specific for the same antigen. Notably, our results indicate that effector function of graft-infiltrating CD4<sup>+</sup> and CD8<sup>+</sup> T cells specific for other β-cell epitopes was significantly impaired, suggesting a novel mechanism of therapeutically induced linked suppression. This work establishes that tolerance induction with a hybrid insulin peptide can delay recurrent autoimmunity in NOD mice, which could inform the development of an Ag-specific therapy for T1D.


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