title: Eosinophils affect functions of in vitro-activated human CD3-CD4+ T cells.
abstract: BACKGROUND
  The recent development of eosinophil-targeting agents has raised enthusiasm for management of patients with hypereosinophilic syndromes. Roughly half of anti-IL-5-treated patients with corticosteroid-responsive lymphocytic (L-HES) and idiopathic disease variants can be tapered off corticosteroids. Potential consequences of corticosteroid-withdrawal on clonal expansion of pre-malignant CD3⁻CD4⁺ T-cells associated with L-HES are a subject of concern. Indeed, corticosteroid treatment inhibits T-cell activation and may lower blood CD3⁻CD4⁺ cell counts. On the other hand, previous studies have shown that eosinophils support CD4 T-cell activation, suggesting that targeted eosinophil depletion may negatively regulate these cells.
  
  
  OBJECTIVE
  Effects of eosinophils on CD4 T-cell activation in vitro were investigated as an indirect means of exploring whether treatment-induced eosinophil depletion may affect pathogenic T-cells driving L-HES.
  
  
  METHODS
  Helper (CD4) T-cells and CD3⁻CD4⁺ cells from healthy controls and L-HES patients, respectively, were cultured in vitro in presence of anti-CD3/CD28 or dendritic cells. Effects of eosinophils on T-cell proliferation and cytokine production were investigated.
  
  
  RESULTS
  Eosinophils enhanced CD3-driven proliferation of CD4 T-cells from healthy subjects in vitro, while inhibiting TCR-independent proliferation and IL-5 production by CD3⁻CD4⁺ T-cells.
  
  
  CONCLUSIONS
  While this study confirms previous work showing that eosinophils support activation of normal helper T-cells, our in vitro findings with CD3⁻CD4⁺ T-cells suggest that eosinophil-depletion may favor activation and expansion of this pathogenic lymphocyte subset. With the ongoing development of eosinophil-targeted therapy for various eosinophilic conditions, the indirect consequences of treatment on the underlying immune mechanisms of disease should be investigated in detail in the setting of translational research programs.
authors: Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.
authors: Issam
authors: I
authors: Harfi
authors: Liliane
authors: L
authors: Schandené
authors: Sarah
authors: S
authors: Dremier
authors: Florence
authors: F
authors: Roufosse
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D017252:CD3 Complex / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D049109:Cell Proliferation; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology; D004804:Eosinophils / Q000166:cytology*; D005786:Gene Expression Regulation; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000166:cytology; D057170:Translational Research, Biomedical
chemical_list: D000305:Adrenal Cortex Hormones; D017252:CD3 Complex; D016207:Cytokines; D015848:Interleukin-5
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