Expression and function of the natural cytotoxicity receptor NKp46 on circulating malignant CD4+ T lymphocytes of Sézary syndrome patients

The natural cytotoxicity receptors NKp30, NKp44, and NKp46 were identified as activating receptors mainly expressed by NK lymphocytes. Here we show that peripheral blood malignant CD4+ T lymphocytes from patients with Sézary 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 to a decreased phosphorylation of the CD3ζ chain associated to 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 Sézary patients, and that its aberrant expression could participate to the pathophysiology of the disease.