Although the ability of CD4 + CD25 + T suppressor (Ts) cells to prevent experimental autoimmune diseases has been described, nothing is known concerning their role and mechanism of action in xenobiotic-induced autoimmunity. Procainamide, mercuric chloride, and gold(I) are three xenobiotics that can induce autoimmune reactions in humans and rodents. After the induction of IgG1 antinuclear autoantibodies (ANA) in mice treated with either of the above xenobiotics, adoptive transfer of their CD4 + CD25 + T cells completely prevented ANA formation in recipients treated with the same xenobiotic; transfer of CD8 + T cells was ineffective. Furthermore, xenobiotic-primed CD4 + CD25 + T cells could also partially prevent ANA formation in recipients treated with a different xenobiotic. CD4 + CD25 -T cells from xenobiotic-treated donors failed to suppress, but induced de novo IgG1 ANA formation in untreated recipients. Our findings suggest that during xenobiotic treatment T cell reactivity may spread from xenobiotic-induced, nucleoprotein-related neoantigens to peptides of the unaltered nucleoproteins.
To analyze T cell cross‐reactivity to para‐compounds, we established CD4+ T cell hybridomas from mice immunized with adducts of self‐globin and one of three different para‐compounds: p‐aminophenol, p‐phenylenediamine, or Bandrowski's base. Some of the hybridomas obtained reacted not only to the immunizing antigen, but also to metabolically related para‐compounds, bound to the same protein, thus suggesting formation of common metabolites. Other hybridomas cross‐reacted to globin adducts of metabolically unrelated para‐compounds, which denotes them as truly cross‐reactive cells whose TCR failed to distinguish among the different haptens. One of these hybridomas also reacted against a non‐haptenated, cryptic peptide of hemoglobin but not to the full‐length native protein. As this hybridoma reacted even more strongly to the respective peptide after it was haptenated, recognition of the native, cryptic peptide was apparently due to true cross‐reactivity. To conclude, true T cell cross‐reactivity to haptens does occur, as well as the formation of a common reactive metabolite, and T cell recognition of cryptic self‐peptides may underlie cross‐sensitization to chemicals.
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