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

X. Zhang, C. S. Schaumburg, T. G. Coursey, K. F. Siemasko, E. A. Volpe, N. B. Gandhi, D. Q. Li, J. Y. Niederkorn, M. E. Stern, S. C. Pflugfelder, C. S. De Paiva

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23 Scopus citations

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 languageEnglish (US)
Pages (from-to)417-427
Number of pages11
JournalMucosal Immunology
Volume7
Issue number2
DOIs
StatePublished - Mar 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Zhang, X., Schaumburg, C. S., Coursey, T. G., Siemasko, K. F., Volpe, E. A., Gandhi, N. B., Li, D. Q., Niederkorn, J. Y., Stern, M. E., Pflugfelder, S. C., & De Paiva, C. S. (2014). CD8+ cells regulate the T helper-17 response in an experimental murine model of sjögren syndrome. Mucosal Immunology, 7(2), 417-427. https://doi.org/10.1038/mi.2013.61