Expression and Function of the Natural Cytotoxicity Receptor NKp46 on Circulating Malignant CD4+ T Lymphocytes of Sezary Syndrome Patients

The natural cytotoxicity receptors NKp30, NKp44, and NKp46 were identified as activating receptors mainly expressed by natural killer (NK) lymphocytes. In this study we show that peripheral blood malignant CD4(+) T lymphocytes from patients with Sezary syndrome, an aggressive form of cutaneous T-cell lymphoma, express NKp46 at their cell surface. Although NKp46 does not behave as an independent functional receptor, its engagement provides a strong inhibiting signal on the malignant T lymphocyte CD3-induced proliferation. We show that this inhibition is correlated with a decreased phosphorylation of the CD3 zeta chain associated with NKp46 and/or the TCR/CD3 complexes. Our results reveal that in addition to KIR3DL2/CD158k expression, NKp46 could represent an additional marker on the circulating malignant T lymphocytes of Sezary patients, where it displays an as yet unreported function of inhibitory co-receptor able to interfere with the processes governing their CD3-dependent proliferation. Journal of Investigative Dermatology (2011) 131, 969-976; doi:10.1038/jid.2010.404; published online 30 December 2010