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Immunomodulatory Effects of Tetrachlorobenzoquinone, a Reactive Metabolite of Hexachlorobenzene
- Source :
- Chemical Research in Toxicology; June 2003, Vol. 16 Issue: 6 p688-694, 7p
- Publication Year :
- 2003
-
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.
Details
- Language :
- English
- ISSN :
- 0893228X and 15205010
- Volume :
- 16
- Issue :
- 6
- Database :
- Supplemental Index
- Journal :
- Chemical Research in Toxicology
- Publication Type :
- Periodical
- Accession number :
- ejs4736419