Jonas Damgård Schmidt
Blegdamsvej 3B, Building: 07-13-16
2200 København N.
Allergy or tolerance
How immune responses to potent contact allergens are regulated
Summary: During our everyday life we are exposed to more and more chemicals. Some of these are allergens that can lead to the induction of contact allergy. The clinical manifestation of contact allergy is allergic contact dermatitis, which is characterized by itching, redness, edema and vesicles, and in severe cases, ulcerations. Contact allergy is the most frequent work related disease in Denmark. Allergic contact dermatitis can have consequences in the form of decreased quality of life, sick-leaves and permanent disabilities which have great social and economic consequences (1;2). In Denmark alone the annual cost for the work related contact allergy is approximately 1 billion Danish crones (3). The most common allergens that induce contact allergy are metals, perfumes, dyes and preservatives (3). The power of these to induce an allergic response varies from non to extreme. A single exposure to some allergens leads to induction of contact allergy in 80-90 % of all exposed individuals (3). In contrast, exposures to other allergens occasional lead to tolerance induction (4;5). Hair dyes are examples of very potent allergens, which can induce various immune regulatory mechanisms. However, the mechanisms that regulate whether an allergen leads to inflammation or induce tolerance are unknown. In this project, I will investigate this by using both mouse models and samples from test subjects. I will investigate the role of allergen concentration, mixture and exposure time on the immune response to a given allergen. Furthermore, I will investigate the role of regulatory T cells (Treg) and interleukin 10 (IL-10) in hair dye-induced tolerance. By improving our knowledge on the regulation of the immune response to contact allergens the perspective of this study is to contribute to the prevention and development of new treatment of allergic disease.
Hypothesis: We suggest that the type of allergen, the exposure time and the cocktail effect obtained by mixing allergens plays an important role in regulating the balance between allergy/inflammation and tolerance.
- Cvetkovski RS, Rothman KJ, Olsen J, Mathiesen B, Iversen L, Johansen JD et al. Relation between diagnoses on severity, sick leave and loss of job among patients with occupational hand eczema. Br J Dermatol 2005; 152(1):93-98.
- Cvetkovski RS, Zachariae R, Jensen H, Olsen J, Johansen JD, Agner T. Quality of life and depression in a population of occupational hand eczema patients. Contact Dermatitis 2006; 54(2):106-111.
- Sundhedsstyrelsen. Forebyggelse af kontakteksem. 17, 1-70. 2001. http://www.sst.dk/Udgivelser/2001/Forebyggelse%20af%20kontakteksemer.aspx, Sundhedsstyrelsen. Forebyggelse og sundhedsfremme.
- Cavani A, Nasorri F, Ottaviani C, Sebastiani S, De PO, Girolomoni G. Human CD25+ regulatory T cells maintain immune tolerance to nickel in healthy, nonallergic individuals. J Immunol 2003; 171(11):5760-5768.
- Artik S, Haarhuis K, Wu X, Begerow J, Gleichmann E. Tolerance to nickel: oral nickel administration induces a high frequency of anergic T cells with persistent suppressor activity. J Immunol 2001; 167(12):6794-6803.