In Vitro Analysis of Proliferating CD4+ T Cells in Patients with Rheumatoid Arthritis as a Possible Predictable Marker of TNF-alpha Blockers
Syuichi Koarada, Yuri Sadanaga, Natsumi Nagao, Satoko Tashiro, Rie Suematsu, Akihide Ohta and Yoshifumi Tada
Affiliation: Division of Rheumatology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
Keywords: Anti-inflammatory drugs, CD4+ T cells, rheumatoid arthritis, IFN-gamma, TNF-alpha, IL-4, Th1, Th2, TNFalpha
blocker, proliferation, APC).
Objectives. To analyze the relationship between in vitro cytokine production in proliferating CD4+ T cells and
the effect of anti-TNF-alpha (tumor necrosis factor-alpha) agents (TNF-alpha blockers) in patients with rheumatoid arthritis
(RA). Methods. Peripheral blood mononuclear cells (PBMCs) from RA patients (n=19) were labeled with CFSE [5
(and 6) carboxyfluorescein diacetate, succinimidyl ester] and cultured with ConA. CD4+ T cells were assessed for production
of IFN-gamma, IL-4 and TNF-alpha, and proliferation by flow cytometry. We examined association of these parameters
with clinical response of TNF-alpha blockers in short, medium and long term studies. Results: Clinically good response
of TNF-alpha blockers was associated with lower TNF-alpha production in proliferating CD4+ T cells in short
term study (p<0.05). Increased production of IFN-gamma (p<0.05) in proliferating CD4+ T cells was associated with
good response in long term study. Conclusions: In vitro evaluation of cytokine production in proliferating CD4+ T cells,
prior to treatment of TNF-alpha blockers, may provide possible information of efficacy of TNF-alpha blockers in RA patients.
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