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<0.05)) and rare types of CTCL (45% FOXP3(+) 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.
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ABSTRACT: CD4(+)CD25(+)FoxP3(+) regulatory T cells (T(reg)) suppress T cell function and protect rodents from autoimmune disease. Regulation of T(reg) during an immune response is of major importance. Enhanced survival of T(reg) is beneficial in autoimmune disease, whereas increased depletion by apoptosis is advantageous in cancer. We show here that freshly isolated FACS-sorted T(reg) are highly sensitive toward CD95-mediated apoptosis, whereas other T cell populations are resistant to CD95-induced apoptosis shortly after isolation. In contrast, TCR restimulation of T(reg) in vitro revealed a reduced sensitivity toward activation-induced cell death compared with CD4(+)CD25(-) T cells. Thus, the apoptosis phenotype of T(reg) is unique in comparison to other T cells, and this might be further explored for novel therapeutic modulations of T(reg).The Journal of Immunology 08/2005; 175(1):32-6. · 5.52 Impact Factor
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ABSTRACT: Primary cutaneous T-cell lymphomas (CTCL) represent a heterogeneous group of neoplasms characterized by skin-homing malignant T-lymphocytes. In contrast to primary extracutaneous (nodal) lymphomas, CTCL is characterized by a prolonged clinical course with a different clinical behavior and outcome. Disease progression, however, involves the recirculation compartments, i.e. lymph nodes and peripheral blood, and may finally spread to the visceral organs. Advances in T-cell receptor gene rearrangement techniques support the clinical diagnosis in early stages of CTCL by improved sensitivity and specificity of molecular diagnosis. The pathogenesis of CTCL is characterized by an altered immune biology and the accumulation of genetic mutations during disease progression. Although there is an initial response to standard therapy, including photochemotherapy, interferons, and retinoids, all patients will eventually relapse, and therefore treatment of CTCL continues to be palliative. New therapeutic drugs including bexarotene, DAB(389)IL-2 and IL-12 have demonstrated clinical responses; and new experimental therapeutic directions, e.g. stem cell transplantation and vaccination strategies may be applied with the intention to cure.Onkologie 11/2003; 26(5):477-83. · 1.00 Impact Factor
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ABSTRACT: Two conferences were sponsored by the International Society for Cutaneous Lymphomas (ISCL) to gain consensus on definitions and terminology for clinical use in erythrodermic cutaneous T-cell lymphoma (E-CTCL). Three subsets of E-CTCL were defined: Sézary syndrome ("leukemic phase" E-CTCL), erythrodermic mycosis fungoides (secondary E-CTCL that develops in patients with mycosis fungoides), and E-CTCL, not otherwise defined. The hematologic criteria recommended for Sézary syndrome are intended to identify patients with a worse prognosis compared with the other E-CTCL subsets and consist of one or more of the following: (1) an absolute Sézary cell count of 1000 cells/mm3 or more; (2) a CD4/CD8 ratio of 10 or higher caused by an increase in circulating T cells and/or an aberrant loss or expression of pan-T cell markers by flow cytometry; (3) increased lymphocyte counts with evidence of a T-cell clone in the blood by the Southern blot or polymerase chain reaction technique; or (4) a chromosomally abnormal T-cell clone. For staging purposes, it is proposed that these criteria define the B2 blood rating and that the B2 rating be considered equivalent to nodal involvement.Journal of the American Academy of Dermatology 02/2002; 46(1):95-106. · 4.91 Impact Factor