title: Brief Report: CD4+ T Cells From Patients With Systemic Lupus Erythematosus Respond Poorly to Exogenous Interleukin-2.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, and Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Denis
authors.initials: D
authors.lastname: Comte
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Karampetsou
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Katalin
authors.initials: K
authors.lastname: Kis-Toth
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Yoshida
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Bradley
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Vasileios C
authors.initials: VC
authors.lastname: Kyttaris
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: George C
authors.initials: GC
authors.lastname: Tsokos
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D020381:Interleukin-17 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology*
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma