Tissue resident memory CD8 + T cells mediate salivary gland damage in a murine model of Sjögren's syndrome.

OBJECTIVE: Although a role for CD4+ T cells in the pathology of Sjögren's syndrome (SS) has been documented, the pathogenic significance of CD8+ T cells is unclear. The aim of this study is to investigate the role of CD8+ T cells in the development of SS.

METHODS: Flow cytometry and immunofluorescence were utilized to detect T cell infiltration within the labial glands of patients with primary SS. In parallel p40-/- CD25-/- mice were used as a murine model of SS. In addition CD4, CD8a and IFN-γ KO mice were crossed with p40-/- CD25-/- mice respectively to study the pathogenic significance of specific lineage subpopulations including functional salivary, histopathological and serological data. CD8+ T cell specific depletion antibody was used to evaluate this potential therapeutic strategy.

RESULTS: CD8+ T cells with tissue resident memory phenotype outnumbered CD4+ T cells in the labial gland of SS patients and were primarily co-localized with saliva duct epithelial cells and acinar cells. Furthermore, infiltrated CD8+ T cells with resident phenotype CD69+ CD103+/- with a significant elevation of IFN-γ production were dominant in the submandibular gland of this SS murine model. CD8a knockout abrogated the development of SS in these mice. Knockout of IFN-γ decreased CD8+ T cell infiltration and gland destruction. More importantly, depletion of CD8+ T cells fully protected mice from SS even after the onset of disease.

CONCLUSIONS: Our data reveal pathogenic significance of CD8+ T cells in the salivary gland pathology in SS. Treatment directed against CD8+ T cells may be a rational therapy for human SS. This article is protected by copyright. All rights reserved.