Immunological abnormality and regulation in patients with Sjögren's syndrome

Abstract

The majority of infiltrating cells into labial salivary glands and into lacrimal glands in patients with Sjogren'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.