1. ¹Immunobiology Department, Division of Immunology, Infection and Inflammatory Disease, King's College London School of Medicine at Guy's, King's College and St Thomas' Hospitals, London, UK
2. ²Skin Tumour Unit, Division of Genetics and Molecular Medicine, St Johns Institute of Dermatology, King's College London School of Medicine at Guy's, King's College and St Thomas' Hospitals, London, UK

Correspondence: Dr Susan John and Dr Leonie S. Taams, Immunobiology Department, King's College London School of Medicine at Guy's, King's College and St Thomas' Hospitals, 2nd Floor New Guy's House, Guy's Campus, St Thomas Street, London SE1 9RT, UK. E-mails: susan.john@kcl.ac.uk, leonie.taams@kcl.ac.uk

³These authors contributed equally to this work.

Received 22 September 2005; Revised 3 April 2006; Accepted 3 April 2006; Published online 1 June 2006.

Abstract

Mycosis fungoides and its leukemic variant, Sezary syndrome, are the most common primary cutaneous T-cell lymphomas (CTCLs). In an ex vivo study, we investigated the percentage, phenotype, and suppressive function of CD4+CD25+ regulatory T cells (Tregs) from peripheral blood of CTCL patients. The percentage of Tregs did not differ significantly between patients and controls. Functional assays demonstrated a dichotomy in Treg function: in four out of 10 patients CD4+CD25+ T cells were incapable of suppressing autologous CD4+CD25- T-cell proliferation, whereas suppressive function was intact in the other six patients. Suppressive activity of Tregs inversely correlated with the peripheral blood tumor burden. T-plastin gene expression, used as a Sezary cell marker, confirmed that Sezary cells were heterogeneous for CD25 expression. Mixed lymphocyte reactions demonstrated that CD4+CD25- T cells from patients who lacked functional Tregs were susceptible to suppression by Tregs from healthy controls, and had not become suppressive themselves. Furthermore, we found reduced expression of Foxp3 in the CD4+CD25+ Tregs of these patients relative to the other six CTCL patients and controls. Our findings thus indicate a dysfunction of peripheral Tregs in certain CTCL patients, which correlates with tumor burden.