Characterization of T Cell Receptor Repertoire and Anti-Ro/SSA Autoantibodies in Relation to Sialadenitis of NOD Mice

Abstract

Non-obese diabetic (NOD) mice develop sialadenitis which morphologically resembles the exocrinopathy in human Sjögren's syndrome (SS). The sialadenitis is characterized by focal infiltrates of inflammatory cells. Immunoenzyme staining (ABC-technique) and monoclonal antibodies defining CD4, CD8, CD11b, TCR α/β, γ/δ, Vβ2, Vβ4, Vβ6, Vβ7, Vβ8.1, 2, Vβ10b and Vβ11 were used to examine the infiltrating mononuclear cells (MNC) in salivary glands of NOD mice. TCR αβ⁺ cells dominated clearly over TCR γδ⁺ cells in the salivary glands. A predominance of CD4⁺ T-cells was identified, while a small population of CD8⁺ cells was found in the salivary gland infiltrates. CD11b⁺ mononuclear cells were sporadically seen within the salivary gland lesions. All different TCR Vβ:s which were analysed appeared to be utilized at the site of MNC infiltration in salivary glands; although with various frequencies. The frequency pattern of Vβ gene expression in salivary glands was Vβ8.1,2 (15%) > Vβ6 (12%) > Vβ4 (11%) > Vβ10b (5%) > Vβ11 (5%) = Vβ2 (5%) > Vβ7 (3%). Analysis of the TCR Vβ utilization in corresponding lymph nodes revealed a quite similar frequency pattern as found in the salivary glands. Serum samples were also tested for anti-Ro52, Ro60 and anti-La antibodies with Western blot. Autoantibody production was limited to anti-Ro/SSA and 3/37 (8%) of the mice were found to produce anti-Ro52 kD antibodies. The degree of sialadenitis (focus score) appeared not to influence reactivity to the Ro52 kD protein.

Key Words:

• NOD
• sialadenitis
• TCR V β
• Ro/SSA antibodies