Genotypic, phenotypic and functional analysis of CD4 + CD7 + and CD4 + CD7 - T lymphocyte subsets in Sézary syndrome

Dummer, Reinhard; Nestle, Frank O.; Niederer, Eva; Ludwig, Elisabeth; Laine, Elisabeth; Grundmann, H. P.; Grob, Peter J.; Burg, Günter

doi:10.1007/s004030050414

Cited by 45 publications

(30 citation statements)

References 31 publications

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“…+ Sézary cells, found in the peripheral blood of a significant number of patients with advanced diseases, 46 are sensitive to galectin-1-mediated cell death. The differential sensitivity to galectin-1-mediated cell death may contribute to the observed accumulation of CD7 − Sézary cells in skin and peripheral blood during progression of the disease.…”

Section: Discussionmentioning

confidence: 99%

CD4+CD7− leukemic T cells from patients with Sézary syndrome are protected from galectin-1-triggered T cell death

et al. 2002

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Section: Discussionmentioning

confidence: 99%

CD4+CD7− leukemic T cells from patients with Sézary syndrome are protected from galectin-1-triggered T cell death

et al. 2002

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“…A different approach to better understand the pathogenesis of Sézary cells, and to distinguish them from normal reactive CD4 ϩ lymphocytes, was to identify characteristic cell membrane receptors. Thus, the immunophenotypic analysis of peripheral blood T cells from patients with SS has revealed a frequent loss of T lymphocyte receptor expression, such as CD7 or CD26, when compared with normal T lymphocytes (7)(8)(9)(10)(11)(12). Recently, we reported the presence of the CD158k/KIR3DL2 inhibitory cell membrane receptor for HLA-A alleles on different CTCL lines established from the skin or the blood of patients with SS (13).…”

Section: Utaneous T Cell Lymphomas (Ctcl)mentioning

confidence: 99%

SC5 mAb Represents a Unique Tool for the Detection of Extracellular Vimentin as a Specific Marker of Sézary Cells

Huet

Bagot

Loyaux

et al. 2006

The Journal of Immunology

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Circulating malignant Sézary lymphocytes result from a clonal proliferation of memory/activated CD4+CD45RO+ T lymphocytes primarily involving the skin. Recently, the CD158k/KIR3DL2 cell surface receptor has been identified to phenotypically characterize these cells. We previously described a mAb termed SC5 that identifies an unknown early activation cell membrane molecule. It is expressed selectively by T lymphocytes isolated from healthy individuals upon activation, and by circulating Sézary syndrome lymphocytes. In addition, we found that SC5 mAb was reactive with all resting T lymphocytes once permeabilized, indicating that SC5 mAb-reactive molecule might present distinct cellular localization according to the T cell activation status. In this study, we show for the first time that SC5 mAb recognizes the intermediate filament protein vimentin when exported to the extracellular side of the plasma membrane of viable Sézary malignant cells. We demonstrate that SC5 mAb is unique as it reacts with both viable malignant lymphocytes and apoptotic T cells. As vimentin is also detected rapidly at the cell membrane surface after normal T lymphocyte activation, it suggests that its extracellular detection on Sézary cells could be a consequence of their constitutive activation status. Finally, as a probable outcome of vimentin cell surface expression, autoantibodies against vimentin were found in the sera of Sézary syndrome patients.

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“…Besides a T-cell memory phenotype, CD4 ϩ CD45RO ϩ , Sézary cells were shown to lack CD26 [3][4][5] and to have diminished CD3 expression, 6 whereas the loss of CD7 3,7 appears not to be a specific feature of the malignant T-cell clone. 5,8 More recently, it has been shown that Sézary cells specifically overexpress T-plastin, which, however, cannot be used as a cell-surface marker because it is located in the cytoskeleton, in association with actin. 9 New markers of Sézary cells were described, including KIR3DL2/CD158k, the first positive cell-surface marker of Sézary cells.…”

Section: Introductionmentioning

confidence: 99%

Significance of circulating T-cell clones in Sézary syndrome

Ortonne

Huet

Gaudez

et al. 2006

Blood

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Identification of malignant Sé zary cells by T-cell receptor (TCR) clonality studies is routinely used for the diagnosis of Sé zary syndrome, but T-cell clones expressed in a single patient have never been accurately characterized. We previously reported that CD158k expression delineates Sé zary syndrome malignant cells, and, more recently, we identified vimentin at the surface membranes of Sé zary cells and normal activated lymphocytes. In the present study, T-cell clones from 13 patients with Sé zary syndrome were identified by immunoscopy and further characterized in the blood according to their TCR V␤, CD158k, and vimentin cell-surface expression. We found in most patients a unique malignant T-cell clone that coexpressed CD158k and vimentin and that, when patients were tested, was also present in the skin. However, in some patients we detected the presence of a nonmalignant circulating clone expressing high amounts of vimentin and lacking IntroductionSézary syndrome (SS) is an erythrodermic, aggressive, cutaneous T-cell lymphoma characterized by a malignant T-cell clone that localizes in the blood and skin. In the absence of a specific marker for malignant Sézary cells, a diagnosis of SS relies on the circulating Sézary cell count and on the molecular detection of a circulating T-cell clone. Given that the cytomorphology of Sézary cells is not specific to SS, 1,2 identification of a specific marker of malignant Sézary cells has been a challenging issue. Besides a T-cell memory phenotype, CD4 ϩ CD45RO ϩ , Sézary cells were shown to lack CD26 3-5 and to have diminished CD3 expression, 6 whereas the loss of CD7 3,7 appears not to be a specific feature of the malignant T-cell clone. 5,8 More recently, it has been shown that Sézary cells specifically overexpress T-plastin, which, however, cannot be used as a cell-surface marker because it is located in the cytoskeleton, in association with actin. 9 New markers of Sézary cells were described, including KIR3DL2/CD158k, the first positive cell-surface marker of Sézary cells. In patients with SS, KIR3DL2/CD158k is dimly expressed by circulating and cutaneous CD4 ϩ lymphocytes. [10][11][12] In healthy persons, CD158k is absent in CD4 ϩ lymphocytes, and only minor subsets of T CD8 ϩ and natural killer (NK) lymphocytes express high amount of this antigen. 13 SC5 monoclonal antibody (mAb) was shown to react with an unknown cell-surface antigen expressed by normal activated lymphocytes and Sézary cells, whereas it failed to stain most circulating T lymphocytes in healthy individuals. 14 We found that SC5 mAb specifically recognizes vimentin (VIM) at the cell surface of viable activated T lymphocytes and is effectively expressed by Sézary cells. 15 The finding of an expanded T-cell clone in the blood of patients with SS is commonly considered to be a diagnostic marker. TCR V␤ phenotyping with specific mAbs may identify a "clonotypic" lymphocyte subset as an expanded population bearing a single TCR V␤ chain, which may be of diagnostic value. 3,[16][17][18] This approach, h...

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Genotypic, phenotypic and functional analysis of CD4 + CD7 + and CD4 + CD7 - T lymphocyte subsets in Sézary syndrome

Cited by 45 publications

References 31 publications

CD4+CD7− leukemic T cells from patients with Sézary syndrome are protected from galectin-1-triggered T cell death

CD4+CD7− leukemic T cells from patients with Sézary syndrome are protected from galectin-1-triggered T cell death

SC5 mAb Represents a Unique Tool for the Detection of Extracellular Vimentin as a Specific Marker of Sézary Cells

Significance of circulating T-cell clones in Sézary syndrome

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