Abstract
Objective
To determine whether eyedrop administration of an anti‐CD4 monoclonal antibody (mAb) is effective in the treatment of Sjögren's syndrome (SS) using a mouse model of the disease.
Methods
The anti‐CD4 mAb was administered daily into the eyes of mice with SS from ages 4 to 8 weeks or ages 10 to 12 weeks. During treatment, tear volume was monitored and after final treatment, histologic features of the lacrimal and salivary glands, the phenotypes and function of T cells, and serum titers of anti–α‐fodrin antibody were examined.
Results
Eyedrop administration of anti‐CD4 mAb before the onset of SS prevented the autoimmune pathology seen in the lacrimal glands but not that in the salivary glands. Furthermore, eyedrop administration of anti‐CD4 mAb after the development of SS inhibited mononuclear cell infiltration and the destruction of parenchyma only in the lacrimal glands. Eyedrop administration of anti‐CD4 mAb suppressed the local activation of CD4+ T cells rather than deleting CD4+ T cells, which reduced the expansion of pathologic CD4+ T cells against α‐fodrin.
Conclusion
These results demonstrate the remarkable efficacy of anti‐CD4 mAb eyedrops in the treatment of SS eye symptoms, which illustrates a new antibody‐based therapeutic strategy for patients with eye problems caused by SS as well as other diseases.