Neonatal stimulation of the thyroid gland with iodine or suppression during adolescence with triiodothyronine changes the prevalence of autoimmune thyroiditis in BB rats

#M-L|#Hartoft-Nielsen|#,; Ak, Rasmussen; Kaas, Anne; Feldt‐Rasmussen, Ulla; Buschard, Karsten

doi:10.1530/eje.0.1510375

“…Furthermore, a different immune response against adult compared to fetal beta cells has been shown (71). The principle of neonatal stimulation in order to diminish later autoimmunity has been extended successfully to the thyroid gland (72). It should be mentioned that to explain the lower risk of T1D in children born of diabetic mothers, compared to offspring of diabetic fathers (70), a beneficial effect of transmission of maternal islet antibodies has also been suggested (73).…”

Section: The Activity Of the Beta Cellsmentioning

confidence: 99%

What causes type 1 diabetes? Lessons from animal models

Buschard

¹

2011

APMIS

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To study type 1 diabetes (T1D), excellent animal models exist, both spontaneously diabetic and virus-induced. Based on knowledge from these, this review focuses on the environmental factors leading to T1D, concentrated into four areas which are: (1) The thymus-dependent immune system: T1D is a T cell driven disease and the beta cells are destroyed in an inflammatory insulitis process. Autoimmunity is breakdown of self-tolerance and the balance between regulator T cells and aggressive effector T cells is disturbed. Inhibition of the T cells (by e.g. anti-CD3 antibody or cyclosporine) will stop the T1D process, even if initiated by virus. Theoretically, the risk from immunotherapy elicits a higher frequency of malignancy. (2) The activity of the beta cells: Resting beta cells display less antigenicity and are less sensitive to immune destruction. Beta-cell rest can be induced by giving insulin externally in metabolic doses or by administering potassium-channel openers. Both procedures prevent T1D in animal models, whereas no good human data exist due to the risk of hypoglycemia. (3) NKT cells: According to the hygiene hypothesis, stimulation of NKT cells by non-pathogen microbes gives rise to less T cell reaction and less autoimmunity. Glycolipids presented by CD1 molecules are central in this stimulation. (4) Importance of the intestine and gliadin intake: Gluten-free diet dramatically inhibits T1D in animal models, and epidemiological data are supportive of such an effect in humans. The mechanisms include less subclinical intestinal inflammation and permeability, and changed composition of bacterial flora, which can also be obtained by intake of probiotics. Gluten-free diet is difficult to implement, and short-term intake has no effect. Regarding the onset of the T1D disease process, slow-acting enterovirus and gliadin deposits are speculated to be etiological in genetically susceptible individuals, followed by the mentioned four pathogenetic factors acting in concert. Neutralization of any one of these factors is capable of stopping T1D development, as lessons are learned from the animal models.

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“…Furthermore, a different immune response against adult compared to fetal beta cells has been shown (71). The principle of neonatal stimulation in order to diminish later autoimmunity has been extended successfully to the thyroid gland (72). It should be mentioned that to explain the lower risk of T1D in children born of diabetic mothers, compared to offspring of diabetic fathers (70), a beneficial effect of transmission of maternal islet antibodies has also been suggested (73).…”

Section: The Activity Of the Beta Cellsmentioning

confidence: 99%

Type-specific human papillomavirus detection in cervical smears in Romania

Anton

¹

,

Peltecu

²

,

Socolov³

et al. 2010

Apmis

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To study type 1 diabetes (T1D), excellent animal models exist, both spontaneously diabetic and virus-induced. Based on knowledge from these, this review focuses on the environmental factors leading to T1D, concentrated into four areas which are: (1) The thymus-dependent immune system: T1D is a T cell driven disease and the beta cells are destroyed in an inflammatory insulitis process. Autoimmunity is breakdown of self-tolerance and the balance between regulator T cells and aggressive effector T cells is disturbed. Inhibition of the T cells (by e.g. anti-CD3 antibody or cyclosporine) will stop the T1D process, even if initiated by virus. Theoretically, the risk from immunotherapy elicits a higher frequency of malignancy. (2) The activity of the beta cells: Resting beta cells display less antigenicity and are less sensitive to immune destruction. Beta-cell rest can be induced by giving insulin externally in metabolic doses or by administering potassium-channel openers. Both procedures prevent T1D in animal models, whereas no good human data exist due to the risk of hypoglycemia. (3) NKT cells: According to the hygiene hypothesis, stimulation of NKT cells by non-pathogen microbes gives rise to less T cell reaction and less autoimmunity. Glycolipids presented by CD1 molecules are central in this stimulation. (4) Importance of the intestine and gliadin intake: Gluten-free diet dramatically inhibits T1D in animal models, and epidemiological data are supportive of such an effect in humans. The mechanisms include less subclinical intestinal inflammation and permeability, and changed composition of bacterial flora, which can also be obtained by intake of probiotics. Gluten-free diet is difficult to implement, and short-term intake has no effect. Regarding the onset of the T1D disease process, slow-acting enterovirus and gliadin deposits are speculated to be etiological in genetically susceptible individuals, followed by the mentioned four pathogenetic factors acting in concert. Neutralization of any one of these factors is capable of stopping T1D development, as lessons are learned from the animal models.

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“…These results reinforce the genetic influence of these autoimmune diseases. Hartoft‐Nielsen et al, however, demonstrated that sodium iodide administered neonatally by injection reduced the incidence of type 1 diabetes and insulitis 26 as well as autoimmune thyroiditis 27 in BB/Worcester rats. The reasons for this discrepancy are not apparent and might be related to factors such as differences in the timing of the treatment (neonates versus weanlings), the method of iodine treatment (injected versus oral), different rat strains, dose and duration of treatment.…”

Section: Discussionmentioning

confidence: 99%