Abstract
Introduction: :
Purposes: We have previously reported that immunization with the molecule kallikrein 1b22 (Klk1b22), cloned from salivary and lacrimal glands, in Lewis rats induced pSS. This study determined whether Klk1b22 can also induce a similar disease in mice.
Methods: :
C57BL/6 (B6) and B10RIII mice were immunized with a recombinant protein of Klk1b22, emulsified in complete Freund’s adjuvant (CFA). pSS was established by expression of clinical symptoms and histology. The cellular and humoral responses to Klk1b22 were assessed by T cell proliferation and antibody assays. The disease inducing ability of Klk1b22 specific T cells and antibody was determined by adoptive transfer of Klk1b22-specific T cells and/or sera from immunized mice to naïve recipients.
Results: :
Immunization of mice with Klk1b22 in CFA induced pSS in B6 recipients but not B10RIII. Decreased tear volume started 28 days post immunization (pi). Immunohistology showed multiple islands of diseased tissue in the lacrimal and salivary glands, with increased cytokeratin positive epimyoepithelial cells and lymphocytes. The majority of infiltrating cells were CD19+ B cells, CD4+ T cells and CD68+ monocytes with few CD8+ cells. Immunized mice exhibited strong T cell responses starting 1 week pi but waned after 3 wks pi. In contrast, anti-Klk1 antibodies were first detected at 2wks pi but persisted for at least 6 wks. Adoptive transfer of either Klk1b22-reactive T cells or immunized sera induced pSS in naïve recipients.
Conclusions: :
An inducible model of pSS has been developed in H-2b B6 mice. This disease model should be very useful to study the mechanism by which the immune response to Klk1b22 results in damage to the exocrine glands.
Keywords: autoimmune disease • lacrimal gland • inflammation