Immunological abnormality and regulation in patients with Sjögren's syndrome

The majority of infiltrating cells into labial salivary glands and into lacrimal glands in patients with Sjögren's syndrome (SS) is CD4⁺TCRab T. Analyses of the T-cell receptor on T cells in both glands support the notion that infiltrating T cells are induced by antigen-driven stimulation. Thus, the identification of autoantigens recognized by T cells in inflamed lesions is important to clarify the pathogenesis of SS. T-cell epitopes on autoantigens in labial salivary glands have been examined using several strategies such as T-cell lines, PCR–single-strand conformational polymorphism, and West-Western methods. Our results showed the following four autoantigens; Ro/SS-A, heat shock protein, α-amylase, and muscarine receptor 3. Especially, the common T-cell epitope on α-amylase in HLA-DR B1*0405-positive SS patients was NPFRPWW-ERYQWPV (amino acids 68–80). The analog peptide of α-amylase might regulate autoimmunity in an antigen-specific fashion.

Furthermore, TCRAV24⁺BV11⁺ double-negative natural killer T (NKT) cells are thought to be regulatory T cells. In patients with SS, these NKT cells are significantly decreased in peripheral blood, inducing the autoimmune response. In vitro stimulation by α-galactosylceramide, which is one of the antigens for NKT cells, was able to enrich NKT cells more than 10–100 times. These findings suggest that the upregulation of NKT cells by α-galactosylceramide might be a new therapeutic strategy in patients with SS.