Injection of CD40 DNA vaccine ameliorates the autoimmune pathology of non-obese diabetic mice with Sjögren's syndrome.

BACKGROUND

Overexpression of CD40 has been reported in patients with primary Sjögren's syndrome (pSS). The increased CD40 expression promote autoimmune response and enhance inflammation in pSS. The aim of this study is to block CD40-CD154 interaction with CD40 DNA vaccine to slow the disease progression of SS in non-obese diabetic (NOD) mice.

METHODS

Female NOD mice were treated with CD40 DNA vaccine, empty vector and normal saline. The salivary flow rate was measured, whereas lymphocytes infiltration in the salivary glands was assessed by histopathology. Expression of CD40 and B220 in salivary were examined by immunohistochemistry. Splenic lymphocyte phenotypes were analyzed by flow cytometry. CD40, IL-1β, TNF-α and IL-6 levels in the salivary glands were detected by PCR. Serum anti-CD40 antibody was measured by ELISA. Serum anti-nuclear antibody (ANA) was monitored by immunofluorescence.

RESULTS

NOD mice treated with CD40 DNA vaccine showed higher levels of anti-CD40 antibody compared with the controls. The expression of CD40 in the salivary glands of NOD mice in CD40 DNA vaccine group was decreased. The infiltration of lymphocytes was reduced in the salivary glands and saliva secretion was increased in the treatment group. The expression level of TNF-α and IL-6 in salivary glands were declined. The splenic dendritic cell and plasma cell populations were reduced and the level of ANA was decreased in NOD mice with CD40 DNA vaccine treatment.

CONCLUSIONS

CD40 DNA vaccine inhibits the immune response and reduce inflammation in epithelial tissues SS in non-obese diabetic (NOD) mice, suggesting that CD40 DNA vaccine could be a new therapeutic approach in treatment of pSS.