Retargeting T Cell-Mediated Inflammation: A New Perspective on Autoantibody Action

• Published in: The Journal of immunology (1950) Vol. 164; no. 10; pp. 5251 - 5257
• Main Authors: Lou, Ya-Huan, Park, Kwan-Kyu, Agersborg, Sally, Alard, Pascale, Tung, Kenneth S. K
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.05.2000
• Subjects: Amino Acid Sequence; Animals; Antibody Specificity; Atrophy; Autoantibodies - administration & dosage; Autoantibodies - physiology; Autoimmune Diseases - etiology; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; Cytokines - physiology; Egg Proteins - administration & dosage; Egg Proteins - immunology; Epitopes, T-Lymphocyte - immunology; Female; Humans; Injections, Subcutaneous; Lymphocyte Transfusion; Membrane Glycoproteins - administration & dosage; Membrane Glycoproteins - immunology; Mice; Mice, Inbred A; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular Sequence Data; Oophoritis - etiology; Oophoritis - immunology; Oophoritis - pathology; Organ Specificity - immunology; Ovarian Follicle - immunology; Ovarian Follicle - pathology; Receptors, Cell Surface; T-Lymphocytes - immunology; T-Lymphocytes - pathology; T-Lymphocytes - transplantation; zona pellucida; Zona Pellucida - immunology; Zona Pellucida - pathology; Zona Pellucida Glycoproteins
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.10.5251

To understand the pathogenesis of organ-specific autoimmune disease requires an appreciation of how the T cell-mediated inflammation is targeted, and how the organ function is compromised. In this study, autoantibody was documented to influence both of these parameters by modulating the distribution of T cell-mediated inflammation. The murine autoimmune ovarian disease is induced by immunization with the ZP3330-342 peptide of the ovarian zona pellucida 3 glycoprotein, ZP3. Passively transferred or actively induced Ab to ZP3335-342 bound to the zona pellucida in the functional and degenerative ovarian follicles, and the ovaries remained histologically normal. Transfer of ZP3330-342 peptide-specific T cells targeted the degenerative follicles and spared the functional follicles, and the resultant interstitial oophoritis was associated with unimpaired ovarian function. Unexpectedly, the coexistence of ZP3330-342 peptide-specific T cells and zona-bound autoantibody led to a dramatic translocation of the ovarian inflammation to the growing and mature ovarian follicles, with destruction of the ovarian functional unit. Ab retargeted both Th1-induced mononuclear inflammation and Th2-induced eosinophilic inflammation, and retargeting was induced by murine and rat polyclonal Abs to multiple distinct native B cell determinants of the zona pellucida. Therefore, by reacting with the native determinants in tissue Ag, Ab alters the distribution of T cell-mediated inflammation, and results in destruction of the functional units of the target organ. We propose that this is a clinically important and previously unappreciated element of Ab action in autoimmune disease.