Abstract
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 Sjögren 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.
Original language | English (US) |
---|---|
Pages (from-to) | 417-427 |
Number of pages | 11 |
Journal | Mucosal Immunology |
Volume | 7 |
Issue number | 2 |
DOIs | |
State | Published - Mar 2014 |
Externally published | Yes |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology