[Objective] Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration of salivary glands, in which CD4+ T cells are predominant. These infiltrating T cells play a crucial role in the generation of SS. We used the RORgt transgenic (Tg) mice, in which transgene expression was driven by hCD2 promoter and spontaneously developed sialadenitis like SS, in order to clarify the pathogenesis of sialadenitis.
[Methods] (1) Infiltrating cells were isolated from the salivary glands and then their character was analyzed by fluorescent immunostaining and FACS. (2) T cells subsets (Th1, Th2, Th17 and Tfh cells) in salivary glands were examined by quantitative PCR. (3) Splenic CD4+ T or CD4- cells from Tg mice were transferred to Rag2-/- mice (CD4+ T or CD4-→Rag2-/- ) and histological analysis was performed. (4) Isolated CD4+ T cells from the salivary glands of Tg mice were transferred to Rag2-/- mice (SG CD4+→Rag2-/-) and infiltrated cells in the salivary glands of SG CD4+→Rag2-/- mice were examined single cell analysis.
[Results] (1) Majority of infiltrating cells was CD4+ T cells at the early phase of sialadenitis, and B cells were gradually increased at late phase. (2) Subset of Th1, Th2, Th17 and Tfh related molecules were increased in salivary glands. (3) In CD4+ T→Rag2-/- mice, sialadenitis was observed, but not in CD4-→Rag2-/- mice. (4) Two dominant TCRβ families were found in the T cells infiltrated in the salivary glands of SG CD4+→Rag2-/- mice. The CDR3 segment sequence was common among each TCRβ family.
[Conclusion] These results suggested that RORgt overexpressed CD4+ T cells play a crucial role in the development of sialadenitis and a specific TCR is involved in the recognition of the salivary gland antigens.