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


CONCLUSIONS
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.
Arakaki
Rieko
R
Tokushima University School of Dentistry, Tokushima, Japan.
Ishimaru
Naozumi
N
Saito
Ichiro
I
Kobayashi
Masaru
M
Yasui
Natsuo
N
Sumida
Takayuki
T
Hayashi
Yoshio
Y
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D051379:Mice; D008817:Mice, Mutant Strains; D008840:Microfilament Proteins / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology; D008969:Molecular Sequence Data; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D013049:Spectrin
D002352:Carrier Proteins; D022801:Complementarity Determining Regions; D008840:Microfilament Proteins; D013049:Spectrin