CD8(+) Cells Regulate the T helper-17 Response in an Experimental Murine Model of Sjögren Syndrome

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.