Open Access Research article

Interleukin-15 and interferon-γ participate in the cross-talk between natural killer and monocytic cells required for tumour necrosis factor production

Isidoro González-Álvaro1, Carmen Domínguez-Jiménez1, Ana M Ortiz1, Vanessa Núñez-González1, Pedro Roda-Navarro23, Elena Fernández-Ruiz2, David Sancho4 and Francisco Sánchez-Madrid4*

Author Affiliations

1 Servicio de Reumatologia, Hospital Universitario de la Princesa, c/ Diego de León 62, 28006 Madrid, Spain

2 Unidad de Biología Molecular, Hospital Universitario de la Princesa, c/ Diego de León 62, 28006 Madrid, Spain

3 Current address: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK

4 Servicio de Inmunologia, Hospital Universitario de la Princesa, c/ Diego de León 62, 28006 Madrid, Spain

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Arthritis Research & Therapy 2006, 8:R88  doi:10.1186/ar1955

Published: 9 May 2006

Abstract

We have characterized the lymphocyte subset and the receptor molecules involved in inducing the secretion of TNF by monocytic cells in vitro. The TNF secreted by monocytic cells was measured when they were co-cultured with either resting or IL-15-stimulated lymphocytes, T cells, B cells or natural killer (NK) cells isolated from the peripheral blood of healthy subjects and from the synovial fluid from patients with inflammatory arthropathies. Co-culture with IL-15-activated peripheral blood or synovial fluid lymphocytes induced TNF production by monocytic cells within 24 hours, an effect that was mainly mediated by NK cells. In turn, monocytic cells induced CD69 expression and IFN-γ production in NK cells, an effect that was mediated mainly by β2 integrins and membrane-bound IL-15. Furthermore, IFN-γ increased the production of membrane-bound IL-15 in monocytic cells. Blockade of β2 integrins and membrane-bound IL-15 inhibited TNF production, whereas TNF synthesis increased in the presence of anti-CD48 and anti-CD244 (2B4) monoclonal antibodies. All these findings suggest that the cross-talk between NK cells and monocytes results in the sustained stimulation of TNF production. This phenomenon might be important in the pathogenesis of conditions such as rheumatoid arthritis in which the synthesis of TNF is enhanced.