Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by infiltration of lymphocytes into lacrimal and salivary glands, and clinically by dry eyes and dry mouth. Auto-antigens recognized by T cells infiltrating the salivary glands of patients with SS have been analyzed, and several candidate auto-antigens such as M3 muscarinic acetylcholine receptor (M3R) have been identified. The presence and specificity of anti-M3R antibodies in patients with SS have been examined [1–3]. We also reported the presence of IFN-c-producing M3R-reactive CD4? T cells in 40% of SS patients with SS [4]. Several studies also detected high levels of IFN-c in the salivary glands of SS patients, and then enhanced activity of T cells, B cells, and macrophages, resulting in the destruction and dysfunction of tissue glands [5, 6]. In contrast, IL-17-producing T cells were also found in salivary glands from patients with SS [7]. Our previous study showed that M3R-reactive T cells were involved in the pathogenesis of sialadenitis using M3R-induced sialadenitis (MIS) mice, which are thought to be model mice for SS. In MIS mice, CD3? T cells were essential for the generation of sialadenitis. Moreover, both

IFN-c and IL-17 were produced by M3R-reactive T cells and were detected in salivary glands, whereas neither IFN-c nor IL-17 was detected in the sera [8]. However, we have no evidence that the cytokines INF-c and/or IL-17 are important in the development of sialadenitis. In the present study, to address the question of whether IFN-c is important in the development of sialadenitis, we generated M3R-/-9IFN-c-/-mice, immunized with M3R peptides, and transferred their splenic cells to Rag-1-/-mice. Histological findings showed that sialadenitis was more severe in M3R-/-9IFN-c-/-? Rag1-/-than that in M3R?/?? Rag1-/- mice, but milder than that in M3R-/-? Rag1-/-mice (Fig. 1 a). Quantitative analysis using histological scores indicated that mononuclear cell infiltration was significantly increased in M3R-/-9IFN-c-/-? Rag1-/-mice compared with that in M3R?/?? Rag1-/- mice (P\0.05), but significantly decreased compared with that in M3R-/-? Rag1-/- mice (P\0.05)(Fig. 1 b). These observations support the notion that IFN-c might play a crucial role in the generation of SS-like sialadenitis. The absence of IFN-c-and presence of IL-17-producing cells in the salivary glands of M3R-/-9IFN-c-/-? Rag1-/-mice were verified by immunohistochemical staining (Fig. 1 c). IL-17-producing cells in inflammatory lesions were identified in both M3R-/-9IFN-c-/-? Rag1-/-and M3R-/-? Rag1-/-mice. IFN-c and IL-17 were not detected in sera from M3R-/-9IFN-c-/-? Rag1-/-mice, nor in M3R-/-? Rag1-/-mice (data not shown). In M3R-/-? Rag1-/-mice, the expression of IL-17 was also observed in salivary glands, as was IFN-c expression. As we have no direct evidence in support of a pathogenic role of IL-17 in MIS, further studies using M3R-/-9IL-17-/-mice will be necessary to clarify the function of IL-17-producing M3R-reactive T cells.