The primacy of CD8 T lymphocytes in type 1 diabetes and implications for therapies

2009 ◽  
Vol 87 (12) ◽  
pp. 1173-1178 ◽  
Author(s):  
Denise L. Faustman ◽  
Miriam Davis
Keyword(s):  
Type 1 Diabetes ◽  
T Lymphocytes ◽  
Cd8 T Lymphocytes

scholarly journals Footprints of Immune Cells in the Pancreas in Type 1 Diabetes; to “B” or Not to “B”: Is That Still the Question?

2021 ◽  
Vol 12 ◽  
Author(s):  
Pia Leete ◽  
Noel G. Morgan
Keyword(s):  
Type 1 Diabetes ◽  
T Lymphocytes ◽  
Beta Cell ◽  
B Lymphocytes ◽  
Immune Cell ◽  
Cell Loss ◽  
Human Type ◽  
Cd8 T Lymphocytes ◽  
Human Type 1 Diabetes

Significant progress has been made in understanding the phenotypes of circulating immune cell sub-populations in human type 1 diabetes but much less is known about the equivalent populations that infiltrate the islets to cause beta-cell loss. In particular, considerable uncertainties remain about the phenotype and role of B-lymphocytes in the pancreas. This gap in understanding reflects both the difficulty in accessing the gland to study islet inflammation during disease progression and the fact that the number and proportion of islet-associated B-lymphocytes varies significantly according to the disease endotype. In very young children (especially those <7 years at onset) pancreatic islets are infiltrated by both CD8+ T- and CD20+ B-lymphocytes in roughly equal proportions but it is widely held that the CD8+ T-lymphocytes are responsible for driving beta-cell toxicity. By contrast, the role played by B-lymphocytes remains enigmatic. This is compounded by the fact that, in older children and teenagers (those ≥13 years at diagnosis) the proportion of B-lymphocytes found in association with inflamed islets is much reduced by comparison with those who are younger at diagnosis (reflecting two endotypes of disease) whereas CD8+ T-lymphocytes form the predominant population in both groups. In the present paper, we review the current state of understanding and develop a proposal to stimulate further discussion of the roles played by islet-associated B-lymphocytes in human type 1 diabetes. We cite evidence indicating that sites of direct contact can be found between CD8+ and CD20+-lymphocytes in and around inflamed islets and propose that such interactions may be important in determining the efficiency of beta cell killing.

scholarly journals Activation of CD4+ and CD8+ T-lymphocytes by insulin and GAD in patients with type 1 or 2 diabetes mellitus

2017 ◽  
Vol 6 (8) ◽  
pp. 758-765 ◽  
Author(s):  
Borros Arneth
Keyword(s):  
Diabetes Mellitus ◽  
T Lymphocytes ◽  
Whole Blood ◽  
Blood Samples ◽  
Cd8 T Lymphocytes ◽  
Type 2 Dm ◽  
Whole Blood Samples ◽  
Type 1 Dm

Background The origin of autoimmune disease type 1 diabetes is still unknown. Aim This study assessed the activation of CD4+ and CD8+ T-lymphocytes by human insulin and human glutamate decarboxylase (GAD) in patients with type 1 or type 2 diabetes mellitus (DM) and healthy volunteers. Materials and methods The expression of CD69, a marker of T-lymphocyte activity, was determined in whole blood samples by flow cytometry after 12 h of incubation with or without insulin or GAD. The analysis included samples from 12 type 1 DM patients, 14 type 2 DM patients and 12 healthy volunteers. Results Significant increases in the number of activated CD4+ and CD8+ T-lymphocytes following pre-incubation of whole blood samples with human insulin or GAD were observed in samples from patients with type 1 DM, whereas no activation of these cells was detected in samples from either type 2 DM patients or healthy subjects. Discussion These results indicated that latent pre-activation of CD4+ and CD8+ T-lymphocytes in response to insulin or GAD epitopes occurred in type 1 DM patients. Conclusion These findings suggest that pre-immunization against insulin and/or GAD might be associated with the development of type 1 DM. Alternatively, these results might reflect a non-specific, bystander autoimmune response.

scholarly journals Development of a Bioconjugate Platform for Modifying the Immune Response of Autoreactive Cytotoxic T Lymphocytes Involved in Type 1 Diabetes

2019 ◽  
Vol 30 (7) ◽  
pp. 2049-2059 ◽  
Author(s):  
Neha Nandedkar-Kulkarni ◽  
Abhishek R. Vartak ◽  
Steven J. Sucheck ◽  
Katherine A. Wall ◽  
Anthony Quinn ◽  
...  
Keyword(s):  
Immune Response ◽  
Type 1 Diabetes ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes

scholarly journals Survival of autoreactive T lymphocytes by microRNA-mediated regulation of apoptosis through TRAIL and Fas in type 1 diabetes

2016 ◽  
Vol 17 (6) ◽  
pp. 342-348 ◽  
Author(s):  
V M de Jong ◽  
A R van der Slik ◽  
S Laban ◽  
R van ‘t Slot ◽  
B P C Koeleman ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Lymphocytes

scholarly journals The targeting ofβ-cells by T lymphocytes in human type 1 diabetes: clinical perspectives

2013 ◽  
Vol 15 (s3) ◽  
pp. 89-97 ◽  
Author(s):  
S. Luce ◽  
C. Briet ◽  
C. Bécourt ◽  
F. Lemonnier ◽  
C. Boitard
Keyword(s):  
Type 1 Diabetes ◽  
T Lymphocytes ◽  
Human Type ◽  
Human Type 1 Diabetes

scholarly journals The role of regulatory CD4+CD25+high T-lymphocytes and their functional activity in the development of type 1 diabetes mellitus

2010 ◽  
Vol 13 (3) ◽  
pp. 25-31
Author(s):  
Tatiana Vasil'evna Nikonova ◽  
Pavel Vasil'evich Apanovich ◽  
Elena Vladimirovna Pekareva ◽  
Vera Anatol'evna Gorelysheva ◽  
Sergey Alexandrovich Prokof'ev ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
T Lymphocytes ◽  
Type 1 Diabetes Mellitus ◽  
Functional Activity ◽  
Risk Group ◽  
Control Group ◽  
Suppressor Activity ◽  
Foxp3 Gene

Type 1 diabetes mellitus (DM1) is associated with compromised (defective) immunologic tolerance to autoantigens and selective destruction of pancreatic B-cells by CD4+ (effector) and CD8 (cytotoxic) lymphocytes. The mechanisms of autotolerance involve CD4+CD25+high T-regulatory cells (Treg) whose suppressor activity depends on the expression of the FoxP3 gene. Aim. Detection of quantitative and functional alterations at the level of regulation of immunity in subjects at risk of DM1 and patients with different duration of DM1. Materials and methods. 116 patients (67 men and 49 women) with different duration of DM1. The risk group was comprised of 33 subjects (10 men and 23 women), control group included 16 subjects. In all cases, HLA genotyping was performed, autoantibodies to GDC, insulin and tyrosine phosphatase, islet cell antigens were determined, subpopulation composition of CD3+, CD4+, CD8+, CD38+, HLA DR+, CD25+, CD4+25+ lymphocytes and their functional activities (FoxP3 gene expression) studied, C-peptie and HbA1c levels measured. Results. A tendency toward a rise in Cd25+ and CD4+25+ T-lymphocytes and a decrease in FoxP3 expression was documented in the risk group compared with control (p0.05) but their functional activity was lower (p

scholarly journals Making the Most of Major Histocompatibility Complex Molecule Multimers: Applications in Type 1 Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Greg S. Gojanovich ◽  
Paul R. Hess
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Subsets ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Pancreatic Islets Of Langerhans

Classical major histocompatibility complex (MHC) class I and II molecules present peptides to cognate T-cell receptors on the surface of T lymphocytes. The specificity with which T cells recognize peptide-MHC (pMHC) complexes has allowed for the utilization of recombinant, multimeric pMHC ligands for the study of minute antigen-specific T-cell populations. In type 1 diabetes (T1D), CD8+ cytotoxic T lymphocytes, in conjunction with CD4+ T helper cells, destroy the insulin-producingβcells within the pancreatic islets of Langerhans. Due to the importance of T cells in the progression of T1D, the ability to monitor and therapeutically target diabetogenic clonotypes of T cells provides a critical tool that could result in the amelioration of the disease. By administering pMHC multimers coupled to fluorophores, nanoparticles, or toxic moieties, researchers have demonstrated the ability to enumerate, track, and delete diabetogenic T-cell clonotypes that are, at least in part, responsible for insulitis; some studies even delay or prevent diabetes onset in the murine model of T1D. This paper will provide a brief overview of pMHC multimer usage in defining the role T-cell subsets play in T1D etiology and the therapeutic potential of pMHC for antigen-specific identification and modulation of diabetogenic T cells.

Sign in / Sign up

Export Citation Format

Share Document