In Vivo Generation of SSA/Ro Antigen-Specific Regulatory T Cells Improves Experimental Sjögren's Syndrome in Mice.

Abstract

Sjögren's syndrome (SS) is a systemic autoimmune disease, and T cells play an important role in the initiation and perpetuation of the disease. In this study, we developed an immunotherapy for NOD/LtJ mice with SS-like symptoms by combining a transient depletion of CD4+ T cells with the administration of autoantigen-specific peptide Ro480. NOD/LtJ mice were treated with single anti-CD4 monoclonal antibody (mAb) followed 2 days later by a series of 6 intraperitoneal injections of Ro480-494 every other day. Salivary flow rates were determined pre- and posttreatment once a week. Mice were euthanized 6 weeks after the initial anti-CD4 mAb treatment, salivary glands (SGs) were collected for analyses of histologic disease scores and inflammatory cell infiltration, polymerase chain reaction determination of genes was conducted, and flow cytometry analysis including major histocompatibility complex class II tetramer staining of immune cells was performed. In addition, adoptive transfer of Treg cells was administrated to investigate the function of the newly generating Treg cells in vivo. The combination of anti-CD4 mAb with autoantigen-specific peptide Ro480 generated SSA/Ro antigen-specific Treg cells in vivo, which can suppress interferon-γ production of CD4+ T cells and inflammation infiltration in SGs and maintain the function of SGs. Our findings provide a new approach to generating antigen-specific Treg cells in vivo for SS treatment, which may have implications for potential therapy for patients with SS.