OBJECTIVE: The pathologic mechanisms responsible for organ-specific tissue damage in primary Sjögren's syndrome (SS) remain unclear, but it has been suggested that the pathology is mediated by autoreactive CD4+ T cells infiltrating the salivary and lacrimal glands. This study was undertaken to investigate whether alpha-fodrin autoantigen-specific autoreactive CD4+ T cells are capable of inducing autoimmune lesions. METHODS: A total of 45 synthetic alpha-fodrin peptides designed to be 20 amino acid residues in length were generated. To establish an autoreactive T cell line, limiting dilution analysis (LDA) was performed on lymph node cells (LNCs) in the presence of alpha-fodrin peptides. The effects of adoptive transfer of autoreactive CD4+ T cells into normal syngeneic recipients were investigated. RESULTS: Autoreactive CD4+ T cell lines that recognize synthetic alpha-fodrin peptide, which produced Th1 cytokines and showed cytotoxic activities, were established in a murine model for SS. T cell receptor V(beta) usage and third complementarity-determining region (CDR3) sequences indicated that in some cases V(beta)6-CDR3 genes matched between the tissue-infiltrating T cells and the autoreactive T cell lines. Adoptive transfer of the autoreactive CD4+ T cells into normal syngeneic recipients induced autoimmune lesions quite similar to those of SS. CONCLUSION: Our data help to elucidate the pathogenic mechanisms responsible for tissue destruction in autoimmune exocrinopathy and indicate that autoreactive CD4+ T cells play a pivotal role in the development of murine SS.
OBJECTIVE: The pathologic mechanisms responsible for organ-specific tissue damage in primary Sjögren's syndrome (SS) remain unclear, but it has been suggested that the pathology is mediated by autoreactive CD4+ T cells infiltrating the salivary and lacrimal glands. This study was undertaken to investigate whether alpha-fodrin autoantigen-specific autoreactive CD4+ T cells are capable of inducing autoimmune lesions. METHODS: A total of 45 synthetic alpha-fodrin peptides designed to be 20 amino acid residues in length were generated. To establish an autoreactive T cell line, limiting dilution analysis (LDA) was performed on lymph node cells (LNCs) in the presence of alpha-fodrin peptides. The effects of adoptive transfer of autoreactive CD4+ T cells into normal syngeneic recipients were investigated. RESULTS: Autoreactive CD4+ T cell lines that recognize synthetic alpha-fodrin peptide, which produced Th1 cytokines and showed cytotoxic activities, were established in a murine model for SS. T cell receptor V(beta) usage and third complementarity-determining region (CDR3) sequences indicated that in some cases V(beta)6-CDR3 genes matched between the tissue-infiltrating T cells and the autoreactive T cell lines. Adoptive transfer of the autoreactive CD4+ T cells into normal syngeneic recipients induced autoimmune lesions quite similar to those of SS. CONCLUSION: Our data help to elucidate the pathogenic mechanisms responsible for tissue destruction in autoimmune exocrinopathy and indicate that autoreactive CD4+ T cells play a pivotal role in the development of murine SS.