Rheumatology Advance Access originally published online on November 15, 2005
Rheumatology 2006 45(4):392-399; doi:10.1093/rheumatology/kei182
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Ex vivo CD4 + T-cell cytokine expression from patients with Sjögren's syndrome following in vitro stimulation to induce proliferation
Division of Rheumatology, Saga Medical School, 5–1–1 Nabeshima, Saga, 849-8501 Japan.
Correspondence to: S. Koarada, Division of Rheumatology, Saga Medical School, 5–1–1 Nabeshima, Saga, 849-8501 Japan. E-mail: koarada{at}med.saga-u.ac.jp
Objective. 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.
Methods. 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-
(IFN-) 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.
Results. The proportion of IFN-+ 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
0.01). The percentage of IFN- 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).
Conclusions. CD4+ T cells from extraglandular SS patients may have a predisposition for entry into the IFN--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.
KEY WORDS: Proliferation, CD4+ T cells, IFN-, Sjögren's syndrome