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IL-4 inhibits IL-2-induced tumoricidal activity and secretory functions of human monocytes. Modulation of IL-2 binding and IL-2 receptor beta gamma chain expression.

M C Bosco, K Pulkki, T K Rowe, A H Zea, T Musso, D L Longo, L Varesio and I Espinoza-Delgado
J Immunol August 1, 1995, 155 (3) 1411-1419;
M C Bosco
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K Pulkki
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T K Rowe
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A H Zea
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T Musso
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D L Longo
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L Varesio
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I Espinoza-Delgado
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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-gamma-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-2R gamma chain above the levels induced by IL-2 alone, whereas it did not significantly affect the expression of IL-2R beta chain. Thus, the inhibition of IL-2 binding by IL-4 may be due to the recruitment of the gamma 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.

  • Copyright © 1995 by American Association of Immunologists

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The Journal of Immunology
Vol. 155, Issue 3
1 Aug 1995
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IL-4 inhibits IL-2-induced tumoricidal activity and secretory functions of human monocytes. Modulation of IL-2 binding and IL-2 receptor beta gamma chain expression.
M C Bosco, K Pulkki, T K Rowe, A H Zea, T Musso, D L Longo, L Varesio, I Espinoza-Delgado
The Journal of Immunology August 1, 1995, 155 (3) 1411-1419;

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IL-4 inhibits IL-2-induced tumoricidal activity and secretory functions of human monocytes. Modulation of IL-2 binding and IL-2 receptor beta gamma chain expression.
M C Bosco, K Pulkki, T K Rowe, A H Zea, T Musso, D L Longo, L Varesio, I Espinoza-Delgado
The Journal of Immunology August 1, 1995, 155 (3) 1411-1419;
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Print ISSN 0022-1767        Online ISSN 1550-6606