Mechanism of self-tolerance and events leading to autoimmune disease and autoantibody response.

Abstract

This review summarizes recent studies on the mechanisms of self-tolerance and autoimmune disease pathogenesis based primarily on the murine ovarian autoimmune disease models. The ovarian autoimmune disease was induced experimentally by three approaches: (1) transfer of normal T cells into syngeneic athymic nu/nu mice, (2) neonatal thymectomy, or (3) immunization with a well-defined peptide from the ovarian antigen, ZP3. Self-reactive T cells with capacity to elicit autoimmune oophoritis and autoimmune gastritis are not deleted in the neonatal or adult thymus. In the adult spleen, T cells are not pathogenic until regulatory T cells have been depleted. Thus the balance of activity between pathogenic T cells and regulatory T cells appears to determine the tolerance status of the host to self-antigens responsible for these autoimmune diseases. Murine autoimmune disease of the ovaries was found to occur through two independent pathways. The first is by depletion of regulatory T cells, as created by thymectomy within 4 days after birth. Alternatively, pathogenic T cells can be activated through molecular mimicry at the level of T cell peptide. This appears to depend on the sharing between non-ovarian and ovarian peptides of critical amino acid residues required for activation of pathogenic T cells. Finally, when T cells that recognize the ZP3 peptide are activated, endogenous ovarian antigens can spontaneously stimulate B cells to produce antibodies that react with ZP3 domains outside the immunizing T cell peptide.

• Authors: K S Tung
• Journal: Clinical immunology and immunopathology (Clin Immunol Immunopathol) Vol. 73 Issue 3 Pg. 275-82 (Dec 1994) ISSN: 0090-1229 [Print] United States
• PMID: 7955555 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Autoantibodies
• Receptors, Antigen, T-Cell

Topics

• Animals
• Autoantibodies (immunology)
• Autoimmune Diseases (immunology)
• Female
• Immune Tolerance
• Mice
• Oophoritis (immunology)
• Ovarian Diseases (immunology)
• Receptors, Antigen, T-Cell (immunology)
• Stomach Diseases (immunology)
• T-Lymphocytes (immunology)