To assess ex vivo CD4(+) T-cell cytokine expression from patients with primary Sjögren's syndrome (SS) following in vitro stimulation to induce proliferation, as proliferation is closely related to differentiation of cytokine-producing cells.
Peripheral blood mononuclear cells (PBMCs) separated from primary SS patients (n = 28) and controls (n = 25) were analysed. PBMCs were stimulated with concanavalin A followed by phorbol 12-myristate 13-acetate and ionomycin. Intracellular interferon-gamma (IFN-gamma) and interleukin-4 (IL)-4 in proliferating CD4(+) T cells were assessed by flow cytometry. The proportion of cytokine-producing cells and proliferating cells in each division cycle was assessed using [5(and 6)-carboxyfluorescein diacetate, succinimidyl ester]-labelled CD4(+/-) T cells.
The proportion of IFN-gamma+ proliferating CD4(+) T cells in each cell division cycle from extraglandular SS was increased in glandular SS patients compared glandular SS patients with controls (P<0.05 approximately 0.01). The percentage of IFN-gamma single positive proliferating CD4(+) T cells was greater in extraglandular SS patients (26.7+/-14.1%) compared with glandular SS (9.9 +/- 9.1%) (P<0.01) and controls (9.4 +/- 5.8%) (P<0.001). There was no significant difference in the percentages of IL-4(+) proliferating CD4(+) T cells among the groups. However, the proliferating response of CD4(+) T cells was significantly decreased in extraglandular SS patients (percentage of proliferating cells 38.4 +/- 18.6%) compared with that in glandular SS patients (64.2 +/- 17.2%) (P<0.05) and controls (63.1+/-10.6%) (P<0.01).
CD4(+) T cells from extraglandular SS patients may have a predisposition for entry into the IFN-gamma-producing effector pathway as a result of the stimulations. These results are helpful for understanding the immunological difference between glandular and extraglandular SS and the mechanisms of disease progression.