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

Arthritis Rheumatol. 2017 Apr;69(4):808-813. doi: 10.1002/art.40014.


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 treatment trials for patients with SLE. Approaches to restore CD4+ T cell sensitivity to IL-2 should be considered.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Humans
  • Interferon-gamma / biosynthesis*
  • Interleukin-17 / biosynthesis*
  • Interleukin-2 / biosynthesis*
  • Interleukin-2 / therapeutic use*
  • Interleukin-4 / biosynthesis*
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / immunology*


  • IL17A protein, human
  • Interleukin-17
  • Interleukin-2
  • Interleukin-4
  • Interferon-gamma