Development of autoimmune exocrinopathy resembling Sjogren's syndrome in adoptively transferred mice with autoreactive CD4+T cells

Objective. The pathologic mechanisms responsible for organ-specific tissue damage in primary Sjogren'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 a-fodrin autoantigen-specific autoreactive CD4+ T cells are capable of inducing autoimmune lesions. Methods. A total of 45 synthetic a-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.