CD8+ CD103+ regulatory T cells attenuate desiccating stress-induced dry eye disease by suppressing CD4+ T cell-mediated inflammation and preserving ocular surface integrity in mice.

OBJECTIVES

This study aimed to investigate the immunomodulatory and protective role of CD8+CD103+ T cells in desiccating stress (DS)-induced dry eye disease (DED), focusing on tear secretion, corneal barrier function, and conjunctival goblet cell preservation.

METHODS

Female C57BL/6 mice were exposed to DS and administered anticholinergic agents to induce experimental DED. CD8+CD103+ T cells were isolated, purified, and adoptively transferred into DS mice. Tear volume was assessed at multiple circadian phases, corneal epithelial integrity was evaluated by fluorescein staining and MMP expression, conjunctival goblet cells were quantified histologically, and apoptosis markers were analyzed. Flow cytometry was performed to assess CD4+ T cell infiltration and cytokine expression profiles.

RESULTS

Adoptive transfer of CD8+CD103+ T cells significantly improved tear secretion across circadian phases, prevented corneal barrier disruption, and preserved goblet cell density. These effects were associated with reduced infiltration of CD4+ T cells in conjunctiva and draining lymph nodes, decreased levels of pro-inflammatory cytokines IFN-γ and IL-17A, and downregulation of MMP-3 and MMP-9. Conversely, IL-13 levels were elevated, correlating with goblet cell protection. Importantly, safety assessments revealed no adverse effects on body weight, intraocular pressure, corneal sensitivity, or corneal nerve density.

CONCLUSIONS

CD8+CD103+ T cells exert immunomodulatory and tissue-protective effects in DS-induced DED by suppressing pathogenic CD4+ T cell responses and restoring a favorable cytokine balance. These findings highlight their potential therapeutic role in ocular surface inflammation and immune-mediated dry eye disease.