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Cutting Edge: Engagement of CD160 by its HLA-C Physiological Ligand Triggers a Unique Cytokine Profile Secretion in the Cytotoxic Peripheral Blood NK Cell Subset¹

Aliz Barakonyi^2,*, Magali Rabot^*, Anne Marie-Cardine, Maryse Aguerre-Girr^*, Beata Polgar^*, Valérie Schiavon, Armand Bensussan^3,4, and Philippe Le Bouteiller^3,4,*

^* Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 563, Centre de Physiopathologie Toulouse-Purpan, Toulouse, France; and INSERM Unité 448, Faculté de Médecine de Créteil, Créteil, France

CD160 is an Ig-like activating NK cell receptor expressed on the majority of circulating NK cells. This population corresponds to the nonproliferating, highly cytolytic, CD56^dimCD16⁺ subset. CD160 engagement by HLA-C molecules mediates cytotoxic function. In this study, we report that upon specific activation by the physiological ligand HLA-C, or Ab cross-linking, CD160⁺ peripheral blood NK cells produce IFN-, TNF-, and IL-6. This unique CD160-mediated cytokine production differs from the one observed after CD16 engagement whose expression is also restricted to the CD56^dim cytotoxic NK cell subset. As already reported for the CD160-mediated cytotoxic effector function, CD160-mediated cytokine production by peripheral blood-NK cells is negatively controlled by the killer Ig-like receptor CD158b. Thus, the CD160 receptor represents a unique triggering surface molecule expressed by cytotoxic NK cells that participates in the inflammatory response and determines the type of subsequent specific immunity.

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