Experimental model of Sjogren’s syndrome accompanied by T lymphocytopenia

Sjogren’s syndrome (SS) is a systemic autoimmune disease characterized by immune-mediated damage to the salivary and lacrimal glands. SS severity and mortality correlate with peripheral CD3 T lymphopenia, which accompanies Sjogren’s syndrome in 5-35% of cases. The mechanism underlying the development of lymphopenia in SS remains unclear. Experimental model is required to study the disease mechanisms. Sjogren’s syndrome model replicates salivary gland damage typical for human primary SS, but does not reproduce lymphopenia symptoms. Sjogren’s syndrome was induced in Wistar rats via intradermal immunization with 10-35 kDa proteins emulsified in CFA, followed by booster injections in CFA and in IFA on days 14 and 28, respectively. The proteins were isolated from homogenized murine salivary glands by size-exclusion chromatography on the SepFast SEC 3-70 sorbent. The numbers of CD3⁺, CD3⁺CD4⁺ and CD3⁺CD8⁺ lymphocytes were determined by flow cytometry. Histological analysis of submandibular salivary gland sections was performed 12 weeks after the initial immunization. The analysis revealed that 33% of rats developed epithelial damage of granular ducts and multiple foci of ductal epithelium hyperplasia. We suggest a transient nature of the induced autoimmune response to the salivary gland antigen since no lymphocytic infiltration was detected in histological analysis. In addition, chronic CD4⁺ and CD8⁺ T cell lymphopenia was detected in 50% of rats immunized with salivary gland proteins. Thus, we have developed an experimental model of Sjogren’s syndrome, which reproduced not only salivary gland damage, but also chronic CD4 and CD8 lymphopenia. This model may serve as a valuable tool for elucidating the mechanisms underlying lymphopenia in Sjogren’s syndrome.