RESEARCH - Neonatal exposure to TCDD causes autoimmunity due to the disruption of T cell tolerance

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J Immunol. 2009 May 15;182(10):6576-86.

Neonatal exposure to low-dose 2,3,7,8-tetrachlorodibenzo-p-dioxin

causes autoimmunity due to the disruption of T cell tolerance.

Ishimaru N, Takagi A, Kohashi M, Yamada A, Arakaki R, Kanno J, Hayashi Y.

Department of Oral Molecular Pathology, Institute of Health

Biosciences, University of Tokushima Graduate School, Kuramotocho,

Tokushima, Japan.

Although 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to

influence immune responses, the effects of low-dose TCDD on the

development of autoimmunity are unclear. In this study, using NFS/sld

mice as a model for human Sjögren's syndrome, in which the lesions are

induced by the thymectomy on day 3 after birth, the autoimmune lesions

in the salivary glands, and in later phase, inflammatory cell

infiltrations in the other organs were developed by neonatal exposure

to nonapoptotic dosage of TCDD without thymectomy on day 3 after

birth. We found disruption of thymic selection, but not thymic

atrophy, in TCDD-administered mice. The endogenous expression of aryl

hydrocarbon receptor in the neonatal thymus was significantly higher

than that in the adult thymus, suggesting that the neonatal thymus may

be much more sensitive to TCDD compared with the adult thymus. In

addition, the production of T(H)1 cytokines such as IL-2 and IFN-gamma

from splenic CD4(+) T cells and the autoantibodies relevant for

Sjögren's syndrome in the sera from TCDD-exposed mice were

significantly increased compared with those in control mice. These

results suggest that TCDD/aryl hydrocarbon receptor signaling in the

neonatal thymus plays an important role in the early thymic

differentiation related to autoimmunity.

PMID: 19414813

http://www.ncbi.nlm.nih.gov/pubmed/19414813

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