title: The role of thymus-dependent T cells in hexachlorobenzene-induced inflammatory skin and lung lesions.
abstract: The involvement of thymus-dependent T cells in the inflammatory skin and lung lesions and spleen effects induced by hexachlorobenzene (HCB) was investigated by using genetically athymic and euthymic WAG/Rij rats and Brown Norway (BN) rats with or without depletion of T cells by adult thymectomy, lethal irradiation, and bone marrow reconstitution. Rats were exposed to diets with no supplementation or diets supplemented with 150 or 450 mg HCB per kg diet for 4 (BN) or 6 (WAG/Rij) weeks. Skin lesion development and body weight gains were assessed during exposure and spleen and liver weights as well as histopathologic changes in skin, lung, and spleen were assessed after exposure. Oral HCB exposure of athymic and euthymic rats of both rat strains resulted in a dose-dependent increase of relative liver weight at doses of 150 and 450 mg/kg HCB and increased relative spleen weights at a dose of 450 mg/kg. HCB exposure of both strains further resulted in inflammatory changes in skin, lungs, and splenic red pulp independent of the T cell status except for skin lesions in the BN strain. HCB-exposed T cell-competent BN rats showed faster skin lesion development than the T cell-depleted rats, although qualitatively and quantitatively similar skin pathology was observed at the end of the 4-week exposure in both groups. In the WAG/Rij strain skin lesions could not be comparatively assessed due to preexistent inflammatory skin pathology in the nude rats. This study showed that thymus-derived T cells are not required for the induction of skin and lung pathology and splenic changes by HCB and therefore it is suggested that HCB acts differently from many allergenic and autoimmunogenic low molecular weight compounds that trigger pathology via thymus-dependent mechanisms. A role for mononuclear phagocytes and, in BN rats, eosinophilic granulocytes, in the HCB-induced pathology is suggested since these cells were prominently present in the HCB-induced lesions.
authors.affiliation: Faculty of Veterinary Medicine, Utrecht University, Ultrecht, The Netherlands.
authors.forename: C C
authors.initials: CC
authors.lastname: Michielsen
authors.forename: N
authors.initials: N
authors.lastname: Bloksma
authors.forename: F A
authors.initials: FA
authors.lastname: Klatter
authors.forename: J
authors.initials: J
authors.lastname: Rozing
authors.forename: J G
authors.initials: JG
authors.lastname: Vos
authors.forename: J E
authors.initials: JE
authors.lastname: van Dijk
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D006579:Heterozygote; D006581:Hexachlorobenzene / Q000633:toxicity*; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D011923:Rats, Nude; D012871:Skin Diseases / Q000139:chemically induced* / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013601:T-Lymphocytes / Q000502:physiology*; D013934:Thymectomy; D013997:Time Factors
chemical_list: D004785:Environmental Pollutants; D006581:Hexachlorobenzene