Eosinophils affect functions of in vitro-activated human CD3-CD4+ T cells

Journal of Translational Medicine

Florence Roufosse³  Sarah Dremier²  Liliane Schandené¹  Issam Harfi² 

[1] Laboratory of Immunology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium;Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium;Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, 808 Route de Lennik, Brussels, B-1070, Belgium

关键词: Anti-IL-5;    Lymphocytic variant hypereosinophilic syndrome;    CD3^-CD4⁺;    CD4 T-cells;    Eosinophil-targeted therapy;   

Others  :  827591
DOI  :  10.1186/1479-5876-11-112

 received in 2012-12-18, accepted in 2013-04-26,  发布年份 2013

【 摘 要 】

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.

Objectives

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.

【 授权许可】

   
2013 Harfi et al.; licensee BioMed Central Ltd.

【 图 表 】

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