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Drug-induced autoantibody formation in mice: triggering by primed CD4+CD25- T cells, prevention by primed CD4+CD25+ T
Laura E Layland1, Marty Wulferink, Sabine Dierkes
1Institut für umweltmedizinische Forschung an der Heinrich-Heine-Universität Düsseldorf gGmbH, Düsseldorf, Germany.
Abstract:
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.
Insights
CD4+CD25+ T suppressor cells prevent xenobiotic-induced autoimmunity by suppressing autoantibody formation. These cells may play a crucial role in managing drug-induced autoimmune reactions.
Area of Science:
- Immunology
- Autoimmunity
- Pharmacology
Background:
- CD4+CD25+ T suppressor (Ts) cells are known to prevent experimental autoimmune diseases.
- The role of Ts cells in xenobiotic-induced autoimmunity remains largely unexplored.
- Certain xenobiotics like procainamide, mercuric chloride, and gold(I) can trigger autoimmune reactions.
Purpose of the Study:
- To investigate the role and mechanism of CD4+CD25+ T suppressor cells in xenobiotic-induced autoimmunity.
- To determine if CD4+CD25+ T cells can prevent the formation of autoantibodies induced by xenobiotics.
- To explore the potential cross-reactivity of xenobiotic-primed T cells.
Main Methods:
- Induction of IgG1 antinuclear autoantibodies (ANA) in mice using procainamide, mercuric chloride, or gold(I).
- Adoptive transfer of CD4+CD25+ T cells and CD8+ T cells from xenobiotic-treated mice into recipients.
- Administration of xenobiotic-primed CD4+CD25+ T cells into recipients treated with a different xenobiotic.
- Transfer of CD4+CD25- T cells from xenobiotic-treated donors into untreated recipients.
Main Results:
- Adoptive transfer of CD4+CD25+ T cells completely prevented ANA formation in recipients treated with the same xenobiotic.
- CD8+ T cell transfer was ineffective in preventing ANA formation.
- Xenobiotic-primed CD4+CD25+ T cells partially prevented ANA formation in recipients treated with a different xenobiotic.
- CD4+CD25- T cells from treated donors failed to suppress but induced de novo ANA formation in recipients.
Conclusions:
- CD4+CD25+ T suppressor cells play a critical role in preventing xenobiotic-induced autoimmunity.
- The findings suggest a mechanism involving T cell reactivity spreading from xenobiotic-induced neoantigens to self-antigens.
- These results have implications for understanding and potentially treating drug-induced autoimmune diseases.
