Location of immunization and interferon-γ are central to induction of salivary gland dysfunction in Ro60 peptide immunized model of Sjögren's syndrome (101.25)

Abstract

Abstract Introduction: Anti-Ro antibodies can be found in the serum of the majority of patients with sjögren's syndrome (SS), which is a chronic autoimmune epithelitis. Immunization with a 60-kDa Ro peptide (Ro60) has been shown to induce SS in mice. The aim of this study was to investigate the mechanism associated with loss of gland activity and optimal conditions and factors involved in salivary gland (SG) dysfunction in this animal model. Methods: Ro60 peptide immunization (either convention or multiple antigenic peptide (MAP)-Ro60) was tested in two strains of mice with or without secondary adjuvant and in different injection sites. Each group of mice was tested for loss of SG function, SG lymphocytic infiltration, anti-Ro and anti-La antibody formation, and cytokine production in cultured cells or homogenized SG extracts. Results: Ro60 peptide immunization in the abdominal area of female Balb/c mice led to impaired SG function, which corresponded with increased Th1 cytokines (IFN-γ and IL-12). Changing the immunization conditions to MAP-Ro60 in the abdominal area also led to impaired SG function in SJL/J mice. As was seen in the Balb/c mice, increased IFN-γ corresponded with SG dysfunction. Conclusions: Effective induction of SG dysfunction after Ro60 peptide immunization depends on the site of injection. The mechanism of action of Ro60 peptide immunization appears to involve an increase in Th1 cytokines, resulting in the induction of SG dysfunction.