IL-4 inhibits IL-2-induced tumoricidal activity and secretory functions of human monocytes: Modulation of IL-2 binding and IL-2 receptor βγ chain expression

M. C. Bosco, K. Pulkki, T. K. Rowe, A. H. Zea, T. Musso, D. L. Longo, L. Varesio, I. Espinoza-Delgado

Research output: Contribution to journalArticlepeer-review

Abstract

Human monocytes express functional IL-2 receptors (IL-2R) and are directly activated by IL-2 to exert effector and secretory functions. In this study, we show that IL-4 selectively suppressed, in a dose-dependent manner, IL-2- induced monocyte tumoricidal activity, without affecting IFN-γ-dependent cytotoxicity. This effect was specific because a neutralizing anti-IL-4 mAb completely restored IL-2-activated cytolysis. Furthermore, IL-4 effectively blocked the secretion of proinflammatory cytokines by IL-2-stimulated monocytes. Binding studies with biotin-conjugated IL-2 demonstrated that monocyte stimulation with IL-2 increased IL-2 binding to the cell surface, and that treatment with IL-4 inhibited this augmentation, providing a possible explanation for the decreased responsiveness of monocytes to IL-2 in the presence of IL-4. However, IL-4 suppressive effects could not be ascribed to the down-regulation of the individual components of the IL-2R complex. In fact, co-treatment of monocytes with IL-2 and IL-4 increased the expression of IL-2Rγ chain above the levels induced by IL-2 alone, whereas it did not significantly affect the expression of IL-2Rβ chain. Thus, the inhibition of IL-2 binding by IL-4 may be due to the recruitment of the γ chain into the IL-4-IL-4R system, making it unavailable for participation in the formation of IL-2 binding sites. These findings provide the first evidence of the ability of IL-4 to suppress IL-2-mediated activation of human monocytes and suggest that IL-4 may play an important role in vivo as an inhibitory signal that controls the response of monocytes to IL-2.

Original languageEnglish
Pages (from-to)1411-1419
Number of pages9
JournalJournal of Immunology
Volume155
Issue number3
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Immunology

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