Lymphoblastoid Interferon-α Inhibits T Cell Proliferation and Expression of Eosinophil-Activating Cytokines

Abstract

T cell-derived cytokines, such as interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) activate eosinophils, whereas other cytokines, such as tumor necrosis factor (TNF)-α and IL-13, determine eosinophil recruitment. Interferon-α (IFN-α), a leukocyte-derived cytokine, has been shown to have beneficial effects in eosinophil-mediated disorders, such as the hypereosinophilic syndrome and a murine model of allergic asthma, where it inhibited eosinophil recruitment. We tested the hypothesis that IFN-α acted in eosinophil-mediated disorders by modulating T cell cytokine expression. Peripheral blood mononuclear cells (PBMC) or human ragweed-specific T_H1 (2B8) and T_H2 (2D2) T cell clones were cultured in the presence of 5 μg/ml of phytohemagglutinin (PHA) or 25 μg/ml of antigen Amb a 1 (short ragweed allergen), respectively, and lymphoblastoid IFN-α (varying from 0 to 10,000 U/ml). We assessed T cell proliferation by [³H]thymidine incorporation and production of IL-5 and GM-CSF by ELISA. Expression of cytokine transcripts was analyzed by the reverse transcription-polymerase chain reaction technique (RT-PCR). IFN-α induced a dose-dependent suppression of T cell proliferation of both PBMC (p < 0.001) and the T cell clones (p < 0.001). IFN-α inhibited gene expression of IL-5, GM-CSF, TNF-α, and IL-13 in PBMC. Furthermore, IFN-α significantly inhibited mitogen-induced and antigen-induced production of IL-5 and GM-CSF. IFN-α may benefit eosinophil-mediated disorders by inhibiting T cell function and production of cytokines active on human eosinophils.