Immunoregulation in Sjögren's syndrome: influence of serum factors on T-cell subpopulations.

21 patients with Sjögren's syndrome (sicca syndrome) with either glandular or extraglandular involvement, but without other connective tissue diseases, were studied with regard to immunoregulatory T-cell subpopulations, B-cell function, and suppressor cell capabilities. Patients with isolated glandular disease as well as patients with extraglandular disease had normal absolute numbers of total lymphocytes, T cells, and B cells. However, 9 of 11 patients with extraglandular disease and only 3 of 10 patients with glandular disease had decreased relative proportions of T cells bearing receptors for the Fc portion of immunoglobulin (Ig)G (T(G)) which was explained by a factor that blocked the expression of the IgG Fc receptor on T(G) cells. This blockage was reversible since the factor could be removed by trypsinizing the T cells before T(G) determination. Serum from patients with abnormal proportions of T(G) cells, but not serum from patients with normal proportions of T(G) cells, blocked the expression of the IgG Fc receptor on normal T cells. The serum factor upon fractionation over Bio-Gel A 1.5 columns as well as over staphylococcal protein A-Sepharose 4B columns was found diffusely within the IgG fraction, and not in the IgM fraction. Neither patients with glandular nor patients with extraglandular disease manifested increased numbers of in vivo-activated circulating lymphocytes as determined by spontaneous anti-trinitrophenyl (TNP) plaque-forming cells (PFC). However, patients with glandular disease had reduced numbers of pokeweed mitogen-induced anti-sheep erythrocyte PFC (P < 0.01) as compared with normals and patients with glandular disease. Of note was the fact that despite the modulation of T(G) subpopulation by the serum factor in patients with extra-glandular disease, these patients manifested normal concanavalin A-generated suppressor cells of pokeweed mitogen-induced PFC responses in allogeneic co-cultures. This was unlike the suppressor cell defect previously described in this system with systemic lupus erythematosus patients. The discrepancy was attributed both to the fact that the T(G) defect was reversible and to the fact that concanavalin A-generated suppressor cells are not limited to the T(G) subset. Thus, these studies have demonstrated reversible abnormalities in T(G) cells in patients with extraglandular Sjögren's syndrome which are not associated with suppressor cell defects. The discrepancy between these findings and the immuno-regulatory defects demonstrated in systemic lupus erythematosus may explain the difference in severity of the autoimmune expression in these diseases.