The role of thymus-dependent T cells in hexachlorobenzene-induced inflammatory skin and lung lesions

The involvement of thymus-dependent T cells in the inflammatory skin and lu ng lesions and spleen effects induced by hexachlorobenzene (HCB) was invest igated by using genetically athymic and euthymic WAG/Rij rats and Brown Nor way (BN) rats with or without depletion of T cells by adult thymectomy, let hal irradiation, and bone marrow reconstitution. Rats were exposed to diets with no supplementation or diets supplemented with 150 or 450 mg HCB per k g diet for 4 (BN) or 6 (WAG/Rij) weeks. Skin lesion development and body we ight gains were assessed during exposure and spleen and liver weights as we ll as histopathologic changes in skin, lung, and spleen were assessed after exposure. Oral HCB exposure of athymic and euthymic rats of both rat strai ns 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 c hanges in skin, lungs, and splenic red pulp independent of the T cell statu s 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 observ ed 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 inflamm atory skin pathology in the nude rats. This study showed that thymus-derive d 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 differe ntly from many allergenic and autoimmunogenic low molecular weight compound s that trigger pathology via thymus-dependent mechanisms. A role for mononu clear phagocytes and, in BN rats, eosinophilic granulocytes, in the HCB-ind uced pathology is suggested since these cells were prominently present in t he HCB-induced lesions. (C) 1999 Academic Press.