Studies on Oral Immune Reactions in the Genetically Mercury-Sensitive BN Rat and in the Hyperplastic BN-(BNxLEW) Graft-versus-Host Disease

Abstract: Mercury (Hg) is known to induce adverse immune reactions in sensitive individuals. e.g. selected inbred animal strains. Such reactions involve oral tissues and may reflect immune phenomena, that may also occur in some human oral diseases. Administration of low doses of HgCl₂ to the genetically Hg-sensitive BN rats results in the development of a syndrome with autoimmune features [BN(Hg)]. inolving oral and perioral tissues. This syndrome seems to be a consequence of the activation of CD4⁺ T cells originally suggested to be autoreactive anti-MHC class II lymphocytes. Lymphocytic infiltration of peripheral tissues and organs similar to changes observed in BN(Hg), may also be provoked by semi-allogeneic "non-chemicaI" activation of the immune system in a hyperplastic [BN-(BNxLEW)] Grafts-versus-Host Disease (GVHD). The general purpose of the present study was to increase our understanding about the nature of the oral immune reactions in BN(Hg). by comparing with the reactions induced in the above-mentioned selected variety of experimental GVHD. The early inflammatory infiltrates in peripheral tissues of both models, as characterised by immunohistochemistry and monoclonal antibodies, were remarkably similar to each other and dominated by RTIB/D⁺ EDI⁺ CD2⁺ and CD4⁺ cells with a smaller number of CD8⁺ and only scarce CD45(240kD)⁺ cells. However in contrast to GVHD, the inflammatory infiltrates in BN(Hg) rats did not cause any apparent tissue destruction. in spite of the variable presence of potential effector, i. e. CD8⁺ and NKR-PI⁺ cells. Furthermore. although the immune syndrome in BN(Hg) is downregulated approximately two weeks after induction, an inconspicuous but persisting population of inflammatory cells was retained in affected penpheral tissues. No correlation between the distribution of tissue-retained mercury and the degree of inflammation was found. It is concluded that the accumulation of mononuclear cells in oral and perioral tissues of HgCl₂-treated BN rats does not represent a local immune response to tissue-retained mercury. Instead, the extravasation may represent an epiphenomenon that is not inevitably deletonous to the infiltrated organs. If this concept is valid in human "diseases". the inflammatory infiltrates found in affected tissues may not necessarily cause any obvious clinical symptoms or functional deficiencies unless the host tissue is compromised in some way. Nevertheless, the potential of these epiphenomena to convert into more aggresive lesions should warrant their early treatment.