Prevention of Diabetes in NOD Mice by Repeated Exposures to a Contact Allergen Inducing a Sub-Clinical Dermatitis

BACKGROUND: Type 1 diabetes is an autoimmune disease, while allergic contact dermatitis although immune mediated, is considered an exposure driven disease that develops due to epicutaneous contact with reactive low-molecular chemicals. The objective of the present study was to experimentally study the effect of contact allergens on the development of diabetes in NOD mice. As the link between contact allergy and diabetes is yet unexplained we also examined the effect of provocation with allergens on Natural Killer T (NKT) cells, since involvement of NKT cells could suggest an innate connection between the two diseases. METHOD: NOD mice 4 weeks of age were exposed, on the ears, to two allergens, p-phenylenediamine and 2,4-dinitrochlorobenzene respectively, to investigate the diabetes development. The mice were followed for a maximum of 32 weeks, and they were either repeatedly exposed to the allergens or only sensitized a week after arrival. The stimulation of NKT cells by the two allergens were additionally studied in C57BL/6 mice. The mice were sensitized and two weeks later provocated with the allergens. The mice were subsequently euthanized at different time points after the provocation. RESULTS: It was found that repeated application of p-phenylenediamine reduced the incidence of diabetes compared to application with water (47% vs. 93%, P = 0.004). Moreover it was shown that in C57BL/6 mice both allergens resulted in a slight increment in the quantity of NKT cells in the liver. Application of the allergens at the same time resulted in an increased number of NKT cells in the draining auricular lymph node, and the increase appeared to be somewhat allergen specific as the accumulation was stronger for p-phenylenediamine. CONCLUSION: The study showed that repeated topical application on the ears with a contact allergen could prevent the development of diabetes in NOD mice. The contact allergens gave a non-visible, sub-clinical dermatitis on the application site. The preventive effect on diabetes may be due to stimulation of peripheral NKT cells, as shown for provocation with p-phenylenediamine in the C57BL/6 mouse. This epicutaneous procedure may lead to new strategies in prevention of type 1 diabetes in humans

Iatrogenic Influences on the Heritability of Childhood Tonsillectomy: Cohort Differences in Twin Concordance

AbstractIn 1980-82, a mailed questionnaire was completed by 3,810 pairs of adult twins enrolled on the Australian NH&amp;MRC Twin Register. Twins were asked whether they had had their tonsils out and, if so, at what age. The sample was divided into four birth cohorts of approximately equal size, and only childhood tonsillectomy (to the age of 18) was considered. The prevalence of tonsillectomy differed markedly between cohorts, being highest in those born in the 1940s and early 1950s. Within each cohort, the prevalence was very similar in MZ and DZ twins, yet concordance was much higher in MZ twins, indicating the importance of genetic factors in predisposition to tonsillectomy. However, the proportions of variance in liability due to genetic and shared environmental factors differed markedly between cohorts. In the 1950s, when tonsillectomy was fashionable, shared environment accounted for 60% of variance and genetic factors for only 29%. However, by the early 1960s, when tonsillectomy was going out of fashion, heritability was up to 0.82 and shared environment accounted for only 10% of variance. Our results illustrate, once again, that heritability is not a constant, but depends on the precise characteristics of the population and the time at which it is studied.</jats:p