T Cell Proliferative Responses of Type 1 Diabetes Patients and Healthy Individuals to Human hsp60 and its Peptides

doi:10.1006/jaut.1998.0262

Journal of Autoimmunity

Volume 12, Issue 2, March 1999, Pages 121-129

https://doi.org/10.1006/jaut.1998.0262 Get rights and content

Abstract

T cell responses to peptide epitopes of the 60 kDa heat shock protein (hsp60) have been shown to play a role in the pathogenesis of type 1 insulin-dependent diabetes mellitus (IDDM) in mice. To test whether hsp60 autoimmunity might be involved in human type 1 diabetes, we studied T cell proliferative responses (stimulation index; SI) to intact human hsp60, to hsp60 peptides and to a recall antigen (tetanus toxoid) in 25 newly diagnosed type 1 diabetes patients, in 22 type 2 (non-insulin-dependent diabetes mellitus, NIDDM) patients, and in 25 healthy blood donors. There were no significant differences between the T cell responses of the three groups to tetanus toxoid. However, the responses to hsp60 of the type 1 diabetes group (median SI=5) were significantly greater (P<0.01) than those of the type 2 group (median SI=1.67) and of the blood donors (median SI=1.7). Epitope mapping revealed significant responses to at least seven different peptides, with prevalent responses to the p277 peptide previously mapped in NOD mice and to peptide p32. Thus, newly diagnosed type 1 diabetes patients, similar to prediabetic and newly diabetic NOD mice, show heightened autoimmunity to hsp60 and hsp60 peptides.

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Cited by (116)

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2016, Canadian Journal of Diabetes
Diabetes is a chronic disease, and its prevalence continues to rise and can increase the risk for the progression of microvascular (such as nephropathy, retinopathy and neuropathy) and also macrovascular complications. Diabetes is a condition in which the oxidative stress and inflammation rise. Heat shock proteins (HSPs) are a highly conserved family of proteins that are expressed by all cells exposed to environmental stress, and they have diverse functions. In patients with diabetes, the expression and levels of HSPs decrease, but these chaperones can aid in improving some complications of diabetes, such as oxidative stress and inflammation. (The suppression of some HSPs is associated with a generalized increase in tissue inflammation.) In this review, we summarize the current understanding of HSPs in diabetes as well as their complications, and we also highlight their potential role as therapeutic targets in diabetes.
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It is well established that post-stroke inflammation contributes to neurovascular injury, blood–brain barrier disruption, and poor functional recovery in both animal and clinical studies. However, recent studies also suggest that several leukocyte subsets, activated during the post-stroke immune response, can exhibit both pro-injury and pro-recovery phenotypes. In accordance with these findings, B lymphocytes, or B cells, play a heterogeneous role in the adaptive immune response to stroke. This review highlights what is currently understood about the various roles of B cells, with an emphasis on stroke risk factors, as well as post-stroke injury and repair. This includes an overview of B cell functions, such as antibody production, cytokine secretion, and contribution to the immune response as antigen presenting cells. Next, evidence for B cell-mediated mechanisms in stroke-related risk factors, including hypertension, diabetes, and atherosclerosis, is outlined, followed by studies that focus on B cells during endogenous protection from stroke. Subsequently, animal studies that investigate the role of B cells in post-stroke injury and repair are summarized, and the final section describes current B cell-related clinical trials for stroke, as well as other central nervous system diseases. This review reveals the complex role of B cells in stroke, with a focus on areas for potential clinical intervention for a disease that affects millions of people globally each year.
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HSPs have been proposed to have a role in the wound healing process, supported by finding that its expression is rapidly induced after skin is wounded in animal models. Because of this phenomenon, we have made a hypothesis that circulating HSPs will have any relationship with DFU.
The circulating levels of HSP 70 and HSP 47 were measured in diabetic patients with an ulcer (Group A: n = 30), without ulcer (Group B: n = 30) and healthy subjects (Group C: n = 30).
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HSP60, an intracellular molecular chaperone has been largely described as an alarmin or damage-associated molecular pattern when released outside the cell. HSP60 has been reported as a possible ligand of TLR2 or TLR4 inducing NFκB-dependant signaling pathway leading to cytokine secretion. However, recent publications suggested that HSP60 could not act as an activator of TLR4 by itself. The observed effect could be due to the presence of endotoxin in HSP60 preparation especially LPS. In order to clarify the controversy, we produced recombinant human HSP60 in two different strains of Escherichia coli, standard strain for protein overproduction, BL21(DE3), and the new ClearColi BL21(DE3) strain which lacks LPS-activity through TLR4. Undoubtedly, we have shown that recombinant HSP60 by itself was not able to induce NFκB-dependant signaling pathway in a model of THP1 monocyte cell line. Our data suggest that HSP60 needs either pathogen-associated molecules, specific post-translational modification and/or other host factors to activate immune cells via NFκB activation.

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^f1: Correspondence to: Irun R. Cohen, Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. Fax: +972 8 9344103. E-mail:[email protected]

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Regular ArticleT Cell Proliferative Responses of Type 1 Diabetes Patients and Healthy Individuals to Human hsp60 and its Peptides

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Regular Article
T Cell Proliferative Responses of Type 1 Diabetes Patients and Healthy Individuals to Human hsp60 and its Peptides