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

This study investigated the regulatory function of CD8(+) cells in T helper-17 (Th17) cell-mediated corneal epithelial barrier disruption that develops in a murine desiccating stress (DS) model that resembles Sjogren syndrome. CD8(+) cell depletion promoted generation of interleukin-17A (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 CC-chemokine attractant ligand 20 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 matrix metalloproteinases (MMP-3 and MMP-9) in the recipient corneal epithelium. Co-transfer of CD8(+)CD103(+) regulatory T cells 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 efferent arm of DS-induced immune response. In summary, CD8(+) regulatory cells suppress generation of a pathogenic Th17 response that has a pivotal role in DS-induced disruption of corneal barrier function.