T cell reactivity to Sjögren's syndrome related antigen La(SSB).

Abstract

Many patients with primary Sjögren's syndrome (SS) make high titer IgG autoantibodies to the La(SSB) antigen, suggesting antigen specific T cell-B cell interactions. T cell responses to some nuclear antigens, particularly U1RNP, have been detected in patients with systemic lupus erythematosus (SLE) and in healthy subjects. We investigated T cell reactivity to the autoantigen SSB in patients with SS and healthy controls. Using the [3H]thymidine proliferation assay, we determined reactivity to purified recombinant SSB (rSSB) in 20 patients with SS and 19 controls. Specificity was determined using tetanus toxoid, endotoxin, and 3 other autoantigens (PBC.M2, Sc170, and GAD). Precursor frequency was calculated by limiting dilution analysis. HLA Class II dependency was investigated using anti-Class II monoclonal antibodies. HLA-DR typing was by polymerase chain reaction and sequence specific oligonucleotide typing. Six of 20 patients with SS and 10/19 controls proliferated to La(rSSB). Precursor frequency of anti-SSB T cells was 1:77,040 and 1:115,000 in 2 healthy subjects and 1:230,250 and 1:103,034 in two patients with SS. Anti-HLA-DR abrogated proliferation to SSB and tetanus toxoid. Thirteen of 15 patients with SS and 4/17 controls were HLA-DR3 positive, with no apparent association of HLA-DR3 with SSB reactivity in controls. Anti-La(SSB) specific T cells occur in a significant proportion of controls and in some patients with SS. The function of SSB T cells in controls remains to be defined. They may represent immunoregulatory cells, and further analysis of these cells, and a comparison to those found in patients with SS, may elucidate normal immunoregulation and the derangements that lead to Sjögren's syndrome.