Perinatal TCDD exposure and the adult onset of autoimmune disease.
Modulation of the developing immune system can occur following perinatal exposure to a number of immunotoxic compounds, including polyhalogenated hydrocarbons like 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD; dioxin), the most toxic of the congeners. Studies in rodents have shown immunologic effects from perinatal TCDD exposure are more severe and persistent than following exposure in the adult, and include what appears to be life-long immunosuppression. Whether prenatal TCDD exposure may predispose an individual to postnatal autoimmune disease remains largely unknown. TCDD crosses the placenta and alters normal prenatal thymocyte maturation, T-cell receptor expression and expression of thymic major histocompatability complex Class II molecules. During the juvenile stage, mice exposed to TCDD prenatally show increased peripheral T-cells possessing "autoreactive" variable-beta receptors. These data suggest that gestational exposure to TCDD may interfere with normal development of central tolerance in the thymus. In possible support of this theory, when autoimmune disease-prone mice were treated with TCDD during gestation, postnatal autoimmunity had an accelerated onset and was exacerbated. This review provides an overview of the currently available information, which appears to support a hypothesis for increased risk of postnatal autoimmune responses as a result of TCDD exposure during the sensitive time of immune system establishment.
Gogal
R M
RM
Center for Molecular Medicine and Infectious Diseases, College of Veterinary Medicine, Virginia Tech University, Blacksburg, VA 24061, USA. rgogal@vt.edu
Holladay
S D
SD
D017668:Age of Onset; D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000276:immunology; D005260:Female; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000196:embryology / Q000503:physiopathology; D038041:Lymphopoiesis / Q000187:drug effects / Q000276:immunology; D018811:Maternal Exposure / Q000009:adverse effects*; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects* / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000276:immunology
D000072317:Polychlorinated Dibenzodioxins