CD8⁺ cells regulate the T helper-17 response in an experimental murine model of Sjögren syndrome.

Abstract

This study investigated the regulatory function of CD8+ cells in T helper (Th) 17 cell-mediated corneal epithelial barrier disruption that develops in a murine desiccating stress (DS) model that resembles Sjögren syndrome. CD8+ cell depletion promoted generation of IL-17A producing CD4+ T cells via activation of dendritic cells in both the ocular surface and draining cervical lymph nodes in C57BL/6 mice subjected to DS. T cell-deficient nude recipient mice receiving adoptively transferred CD4+ T cells from CD8+ cell-depleted donors exposed to DS displayed increased CD4+ T cell infiltration and elevated IL-17A and CCL20 levels in the ocular surface, which was associated with greater corneal barrier disruption. Enhanced DS-specific corneal barrier disruption in CD8-depleted donor mice correlated with a Th17-mediated expression of matrixmetalloproteinases (MMP-3 and MMP-9) in the recipient corneal epithelium. Co-transfer of CD8+ CD103+ Tregs did not affect the ability of DS-specific pathogenic CD4+ T cells to infiltrate and cause ocular surface disease in the nude recipients, showing that CD8+ cells regulate the afferent arm of DS-induced immune response. In summary, CD8+ regulatory cells suppress generation of a pathogenic Th17 response that plays a pivotal role in DS-induced disruption of corneal barrier function.