ANTI-120-KDA ALPHA-FODRIN IMMUNE-RESPONSE WITH TH1-CYTOKINE PROFILE IN THE NOD MOUSE MODEL OF SJOGRENS-SYNDROME

Our recent study suggested that the 120-kDa alpha-fodrin molecule may be an important autoantigen in the pathogenesis of Sjogren's syndrome, and anti-120-kDa alpha-fodrin antibodies have been detected in patien ts with Sjogren's syndrome. Here we have analyzed anti-120-kDa alpha-f odrin immune responses during development of spontaneous autoimmune si aladenitis in NOD mice as a model of Sjogren's syndrome. We found spec ific autoantibody production against 120-kDa alpha-fodrin, and its pro duction correlated closely with autoimmune sialadenitis. A specific T cell response of splenocytes against the 120-kDa alpha-fodrin autoanti gen was observed in NOD mice from the early onset of autoimmune sialad enitis. In addition, production in vitro by splenic T cells of cytokin es such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), but not IL-4, was detected by enzyme-linked immunosorbent assays, We found upregulation of local cytokine genes, including those of Th1 type (IL -1 beta, TNF-alpha, IL-2, IFN-gamma, IL-6), as well as IL-10 and IL-12 (p40), in the tissue-infiltrating cells during the course of autoimmun e sialadenitis. These findings suggest that in spontaneous autoimmune sialadenitis in NOD mice, there may be a specific anti-120-kDa alpha-f odrin immune response in the development of autoimmune lesions resembl ing human Sjogren's syndrome, and that the autoreactive Th1 cells poss ess an up-regulated cytokine profile besides IL-10 and IL-12.