Demonstration of a TH1cytokine profile in the late phase of NOD insulitis

Pilström, Björn; Björk, Lars; Böhme, Jan

doi:10.1006/cyto.1995.0097

Cited by 37 publications

(26 citation statements)

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“…This pattern of chemokine content correlates with the presence of a Th1-enriched environment in the pancreas at diabetes onset (30 -32), consistent with the presence of a higher IFN-␥:IL-4 concentration ratio in the pancreata of diabetic female NOD mice than in nondiabetic NOD mice (31,32). Collectively, these findings implicate a temporal relationship between a higher intrapancreatic MIP-1␣:MIP-1␤ ratio and the development of destructive insulitis and overt diabetes in NOD mice.…”

Section: Discussionsupporting

confidence: 56%

Differential Expression of CC Chemokines and the CCR5 Receptor in the Pancreas Is Associated with Progression to Type I Diabetes

Cameron

Arreaza

Grattan

et al. 2000

The Journal of Immunology

134

107

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We investigated the biological role of CC chemokines in the Th1-mediated pathogenesis of spontaneous type I diabetes in nonobese diabetic (NOD) mice. Whereas an elevated ratio of macrophage inflammatory protein-1α (MIP-1α):MIP-1β in the pancreas correlated with destructive insulitis and progression to diabetes in NOD mice, a decreased intrapancreatic MIP-1α:MIP-1β ratio was observed in nonobese diabetes-resistant (NOR) mice. IL-4 treatment, which prevents diabetes in NOD mice by polarizing intraislet Th2 responses, decreased CCR5 expression in islets and potentiated a high ratio of MIP-1β and monocyte chemotactic protein-1 (MCP-1): MIP-1α in the pancreas. Furthermore, NOD.MIP-1α−/− mice exhibited reduced destructive insulitis and were protected from diabetes. Neutralization of MIP-1α with specific Abs following transfer of diabetogenic T cells delayed the onset of diabetes in NOD.Scid recipients. These studies illustrate that the temporal expression of certain CC chemokines, particularly MIP-1α, and the CCR5 chemokine receptor in the pancreas is associated with the development of insulitis and spontaneous type I diabetes.

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Section: Discussionsupporting

confidence: 56%

Differential Expression of CC Chemokines and the CCR5 Receptor in the Pancreas Is Associated with Progression to Type I Diabetes

Cameron

Arreaza

Grattan

et al. 2000

The Journal of Immunology

134

107

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“…This is based on the following observations: (i) induction of MHC class II expression (as well as expression of Fas and TNFR2) comes along with the occurrence of insulitis; (ii) in 9-to 10-weekold NOD/SCID mice, the islets of which are free of any lymphocytic infiltration, beta cells express MHC class II mRNA at the same low frequency as beta cells from insulitis-free islets of NOD mice of 3 weeks of age (excluding the possibility that MHC class II expression is a developmental event); (iii) TNF-α and IFN-γ have been shown to be expressed by infiltrating cells [23]; (iv) these cytokines have been shown to be able to trigger expression of MHC class II on beta cells in vitro [6,11]. In the same way TNFR2 and Fas could be triggered by these cytokines, possibly in concert with IL-1 (also known to be expressed by islet-infiltrating cells early in pathogenesis [23]) in the case of Fas.…”

Section: Discussionmentioning

confidence: 99%

Pancreatic NOD beta cells express MHC class II protein and the frequency of I-Ag7 mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes

et al. 2003

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Aims/hypothesis. In the NOD mouse model, attempts to show MHC class II expression by pancreatic beta cells were unsuccessful so far. We readdressed this question by analysing I-A g7 expression in single pancreatic beta cells. Methods. Single-cell multiplex RT PCR and singlecell immunofluorescence were used to study MHC class II expression in NOD and NOD/SCID beta cells. Results. Pancreatic beta cells from NOD mice express the I-A g7 protein as well as the corresponding mRNA. The frequency of MHC class II mRNA-expressing beta cells is drastically increased during the progression to overt diabetes. MHC class II protein is accumulated intracellularly, and invariant chain is co-expressed.

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“…During a later phase of insulitis, there is a characteristic type 1 T helper cytokine profile, with production of IFN-g occurring after stimulation [28]. IFN-g has been detected in lymphocytes infiltrating the islets of humans with recent onset Type I diabetes.…”

Section: Discussionmentioning

confidence: 99%

Ingested interferon α suppresses Type I diabetes in non-obese diabetic mice

Brod¹,

Malone²,

Darcan³

et al. 1998

Diabetologia

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Many key features of human Type I diabetes are reflected in the non-obese diabetic (NOD) mouse model. These include the development of insulitis, with infiltration of lymphocytes that are selectively cytotoxic to the insulin producing beta cells into the pancreatic islets of Langerhans, the dependence of disease pathogenesis by T cells, and the transmission of Type I diabetes by haematopoietic cells in bone marrow [1±5].Experimental autoimmune encephalomyelitis (EAE) is an animal model for the presumed autoimmune disease multiple sclerosis. We have previously shown that ingested type 1 interferon (IFN) inhibits chronic relapsing EAE, inhibits the adoptive transfer of EAE by T cells, decreases both antigen-specific and mitogen-induced pro-inflammatory cytokine secretion and decreases serum soluble intercellular adhesion molecule 1 (sICAM-1) levels, a marker for subclinical disease activity, in multiple sclerosis without the absorption of ingested IFN [6±8].The NOD mouse [9±11] model is mechanistically analogous to the EAE animal model because both are presumed to be mediated by a T cell subset, and depend on restriction elements and inflammatory cy- Diabetologia (1998) Summary Type I diabetes mellitus is a chronic disorder that results from autoimmune destruction of the insulin-producing pancreatic beta cell. The nonobese diabetic mouse is a model of the human autoimmune disease Type I diabetes [1±3]. We have previously shown that ingested type 1 interferon inhibits chronic relapsing experimental autoimmune encephalomyelitis and the adoptive transfer of experimental autoimmune encephalomyelites by T cells, and decreases both antigen-specific and mitogen-induced pro-inflammatory cytokine secretion in this disorder. We therefore tried to determine whether ingested murine interferon a inhibits insulinitis and suppresses Type I diabetes mellitus in non-obese diabetic mice. Murine interferon a, given daily, decreased islet inflammation and suppressed diabetes. It increased the concanavalin A and ionomycin plus myristic acid palmitic ester-induced production of interleukin 4 and 10 and interferon g-secretion in spleen cells from treated mice. Adoptive transfer of unstimulated splenocytes secreting interleukin 4 and interleukin 10 from fed interferon a donors suppressed spontaneous diabetes mellitus in recipients. The protective effect of adoptively transferred unstimulated splenocytes shows the presence of ingested interferon a-activated regulatory splenic cell populations that may work via increased interleukin 4 or interleukin 10 production. Ingested interferon a administered during vulnerable periods in at-risk populations may potentially provide a continuous, convenient, non-toxic and effective treatment for Type I diabetes. [Diabetologia (1998) 41: 1227±1232]Keywords Non-obese diabetic mouse, ingested interferon a, interleukin 4, interleukin 10, adoptive transfer

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Demonstration of a TH1cytokine profile in the late phase of NOD insulitis

Cited by 37 publications

References 0 publications

Differential Expression of CC Chemokines and the CCR5 Receptor in the Pancreas Is Associated with Progression to Type I Diabetes

Differential Expression of CC Chemokines and the CCR5 Receptor in the Pancreas Is Associated with Progression to Type I Diabetes

Pancreatic NOD beta cells express MHC class II protein and the frequency of I-Ag7 mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes

Ingested interferon α suppresses Type I diabetes in non-obese diabetic mice

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