The present study of the regulatory T phenotype of Sézary cells led to the discovery of the overexpression of CD81 by Sézary cells. CD81 has also been shown to be a relevant therapeutic target in the treatment of Sézary syndrome, NK/T lymphoma, hepatosplenic T-cell lymphoma and acute T cell leukemia. CD81 therefore appears as a diagnostic marker and as a therapeutic target in T-cell malignancies. Accordingly, the present invention relates CD81 as a biomarker and biotarget in T-cell malignancies.