Brief Report: CD4+ T Cells From Patients With Systemic Lupus Erythematosus Respond Poorly to Exogenous Interleukin‐2

作者：Denis Comte, Maria P. Karampetsou, Katalin Kis‐Tóth, Nobuya Yoshida, Sean J. Bradley, Vasileios C. Kyttaris, George C. Tsokos · 发表于：Arthritis & Rheumatology · 年份：2016 · DOI：10.1002/art.40014 · 被引用次数：61 · 研究领域：Systemic Lupus Erythematosus Research、Psoriasis: Treatment and Pathogenesis、T-cell and B-cell Immunology

OBJECTIVE: Imbalanced cytokine production by T cells characterizes both patients with systemic lupus erythematosus (SLE) and lupus-prone mice and contributes to immune dysregulation. This study was undertaken to further investigate in detail the production of interleukin-2 (IL-2), interferon-γ (IFNγ), IL-4, and IL-17A by CD4+ cell subsets in healthy subjects and patients with SLE, and the signaling response of CD4+ T cells in response to exogenous IL-2. METHODS: Cytokine production by differentiated subsets of CD4+ T cells was assessed by intracellular staining following stimulation with phorbol myristate acetate and ionomycin and by enzyme-linked immunosorbent assay after anti-CD3/anti-CD28 stimulation. The IL-2 signaling pathway was examined by assessing JAK-3/STAT-5 phosphorylation. Cell proliferation in response to IL-2 was examined by carboxyfluorescein succinimidyl ester dilution. RESULTS: Production of IL-2 was defective primarily among naive CD4+ T cells, whereas the production of IFNγ, IL-4, and IL-17A was not significantly different between patients with SLE and healthy subjects. JAK-3/STAT-5 phosphorylation and proliferation of CD4+ T cells from SLE patients in response to exogenous IL-2 were impaired compared to cells from healthy subjects. CONCLUSION: These data suggest that altered IL-2 production, as well as impaired IL-2-mediated signaling and proliferative responses, characterize SLE CD4+ T cells. Our data demonstrate the need for caution in designing IL-2 tr...