Paucity of FOXP3+ cells in skin and peripheral blood distinguishes Sézary syndrome from other cutaneous T-cell lymphomas

Abstract

Cutaneous T-cell lymphomas (CTCL) are mainly comprised of two variants: mycosis fungoides (MF) with CD4⁺ tumor cells confined to the skin and the leukemic Sézary syndrome with tumor cell spread to the blood. In this study, we investigated cutaneous expression of the regulatory T-cell (T_reg) marker FOXP3 in 30 CTCL patients. Immunohistochemical analysis revealed significantly lower numbers of CD4⁺FOXP3⁺ cells within the dermal lymphomononuclear infiltrate of Sézary patients (16% FOXP3⁺ cells of CD4⁺ cells) in contrast to MF (43% FOXP3⁺ cells (P+ cells). Furthermore, CD4⁺FOXP3⁺ T cells were also markedly reduced in the CD4⁺ population within the peripheral blood of Sézary patients compared to controls as determined by fluorescence-activated cell sorter, quantitative PCR and functional analyses. The data support the conclusion that the neoplastic cells in CTCL do not express the T_reg marker FOXP3. Our data also identify Sézary syndrome as, to our knowledge, the first reported neoplastic disease with a clear reduction in T_reg numbers within the CD4⁺ population. This lack of T_reg might account for the more aggressive nature of Sézary syndrome compared with other CTCL.