1. Immunomodulatory effects of tetrachlorobenzoquinone, a reactive metabolite of hexachlorobenzene.
- Author
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Ezendam J, Vissers I, Bleumink R, Vos JG, and Pieters R
- Subjects
- Animals, Antibody Formation drug effects, Autoimmunity immunology, Cell Count, Female, Flow Cytometry, Hydroquinones toxicity, Immunohistochemistry, Local Lymph Node Assay, Lymph Nodes immunology, Lymph Nodes pathology, Lymphocyte Subsets drug effects, Lymphocyte Subsets pathology, Mice, Mice, Inbred BALB C, Adjuvants, Immunologic toxicity, Autoimmunity drug effects, Chloranil toxicity, Fungicides, Industrial toxicity, Hexachlorobenzene metabolism, Lymph Nodes drug effects
- Abstract
Hexachlorobenzene (HCB) is an environmental pollutant that causes autoimmune-like effects in humans and rats. It is not completely clear whether T cells are involved and, if so, how they are stimulated after oral exposure to HCB. HCB as a rather inert chemical is not likely to bind covalently to macromolecules. The oxidative metabolite of HCB, tetrachlorobenzoquinone (TCBQ), which is in a redox equilibrium with tetrachlorohydroquinone (TCHQ), can bind to macromolecules, hence may form hapten-carrier complexes in vivo. We have assessed in the reporter antigen-popliteal lymph node assay whether HCB or TCHQ and TCBQ are able to induce a 2,4,6-trinitrophenyl (TNP) specific IgG1 response to the T cell-independent antigen TNP-Ficoll, which is indicative of neoantigen specific T cell help. To this end, these compounds and silica were injected into the footpad of Balb/c mice. Silica was included as an inert model compound, which causes autoimmune-like effects by activating macrophages. Seven days later, cell number and TNP specific antibody-secreting cells (ASC) in the popliteal lymph node (PLN) were determined. Furthermore, a secondary PLNA was performed to find out if TCHQ was capable of eliciting a memory response. Silica, TCHQ, and TCBQ, but not HCB, increased PLN cellularity and the number of IgM-producing ASC by ELISPOT. Both oxidative metabolites were able to induce the formation of germinal centers as assessed by immunohistochemistry and an IgG1 response to TNP-Ficoll. In the secondary PLNA, only mice primed with TCHQ and challenged with TCHQ together with TNP-Ficoll showed a significant increase in TNP specific IgG1 ASC. Present data show that TCHQ and TCBQ are capable of inducing neoantigen specific T cell help and that TCHQ can induce a compound specific memory response.
- Published
- 2003
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