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

Rappl, Gunter; Abken, Hinrich; Jm, Muche; Sterry, Wolfram; Tilgen, Wolfgang; André, Sabine; Kaltner, Herbert; Ugurel, Selma; Gabius, Hans‐Joachim; Reinhold, Uwe

doi:10.1038/sj.leu.2402438

Cited by 101 publications

(81 citation statements)

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“…Although the CD7 ϩ cell line HH was modestly susceptible to galectin-1-induced cell death, another CD7 ϩ cell line, SeAx/i, was not susceptible to galectin-1. These findings support the hypothesis that the absence of CD7 is one important factor mediating the reduced sensitivity of Sezary cells to apoptosis via galectin-1 (38). However, additional factors, i.e., changes in cell surface glycosylation, may also contribute to Sezary cell resistance to galectin-1 death.…”

Section: Discussionsupporting

confidence: 78%

“…In addition to the CD7 polypeptide, galectin-1-mediated T-cell apoptosis requires the expression of specific saccharide ligands that are present on a subset of glycoprotein receptors, including CD7 (36). A recent report examined a panel of Sezary cell lines and correlated lack of CD7 expression with resistance to galectin-1-induced apoptosis (38). However, tumor cells are known to have aberrant patterns of cell surface glycosylation, a feature that contributes to the malignant phenotype (39).…”

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confidence: 99%

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Galectin-1–Mediated Apoptosis in Mycosis Fungoides: The Roles of CD7 and Cell Surface Glycosylation

et al. 2003

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Sezary cells, the malignant T cells in mycosis fungoides/Sezary syndrome, resist a variety of apoptosis-inducing agents, a feature that contributes to the poor response to therapy in mycosis fungoides. Galectin-1 is a mammalian lectin that triggers T cell apoptosis. For T cells to be susceptible to galectin-1-induced apoptosis, the T cells must express specific glycoprotein receptors, such as CD7, that bear the specific oligosaccharides recognized by galectin-1. Because Sezary cells are characteristically CD7 ؊ , lack of CD7 expression has been proposed to render Sezary cells resistant to galectin-1-induced death. However, the role played by aberrant cell surface glycosylation in resistance of Sezary cells to galectin-1 has not been examined. In this study, we demonstrated abundant galectin-1 in mycosis fungoides skin lesions, indicating that Sezary cells are exposed to galectin-1 in vivo. To determine specific characteristics of Sezary cells that contribute to galectin-1 resistance, we assessed CD7 expression and cell surface glycosylation of Sezary cells in mycosis fungoides lesions and of four Sezary T cell lines. Sezary cells in primary lesions and Sezary T cell lines demonstrated a characteristic "glycotype" with sialylated core 1 O-glycans that promote galectin-1 resistance. Expression of CD7 was necessary but not sufficient for galectin-1-induced death of Sezary cell lines. In addition, CD7 ؊ Sezary cell lines, and Sezary cells within mycosis fungoides lesions, expressed galectin-1, whereas CD7-positive Sezary cell lines did not express galectin-1. We propose that both loss of CD7 expression and altered cellular glycosylation contribute to apoptosis resistance of malignant T cells in mycosis fungoides.

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Section: Discussionsupporting

confidence: 78%

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confidence: 99%

Galectin-1–Mediated Apoptosis in Mycosis Fungoides: The Roles of CD7 and Cell Surface Glycosylation

et al. 2003

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“…T-cell CD7 gene transcription has been shown to be induced by non-mitogenic ionomycin-induced transmembrane calcium flux. 22 Knowing that CD7 delivers a pro-apoptotic signal during galectin-1-induced Tcell death 10 and that CD4 þ CD7 À leukemic T cells from patients with Sezary syndrome are protected from galectin-1-triggered Tcell death, 11 we went back to our micro-arrays data. Some of the calcium-related genes progressively downregulated after HTLV-I infection are implicated in apoptosis: PLA2G4A, 36 ITPR1 and ITPR2.…”

Section: Discussionmentioning

confidence: 99%

“…Although intracellular galectin-3 blocks T-cell death, 31 the CD4 þ CD7 À leukemic T-cells from patients with Sezary syndrome were protected from galectin-1-triggered T-cell apoptosis. 11 This suggests that the Figure 3 (a) Supershift analysis of NFAT and NF-kB to the NFAT g1 and NFAT g2 probes 32 P-labeled NFAT g1 and NFAT g2 probes were used in a supershift assay with nuclear extracts from CD3 þ CD7 þ HTLV-1-infected cells in the absence of antibodies (lanes 1 and 6) or in the presence of anti-NFATc2 (lanes 2 and 7), anti-NFATc1 (lanes 3 and 8), anti-NF-kB p50 (lanes 4 and 9) and free probe (lanes 5 and 10). (b) Correlation between TCR/CD3 and CD7 surface expression and binding of NFATc1, NFATc2 and NF-kB p50 to the NFAT g1 and NFAT g2 probes.…”

Section: Apoptosis-related Genes Expression In Htlv-i-infected Cellsmentioning

confidence: 99%

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HTLV-I infection of WE17/10 CD4+ cell line leads to progressive alteration of Ca2+ influx that eventually results in loss of CD7 expression and activation of an antiapoptotic pathway involving AKT and BAD which paves the way for malignant transformation

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et al. 2007

Leukemia

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Adult T-cell leukemia/lymphoma (ATLL) is a malignancy slowly emerging from human T-cell leukemia virus type 1 (HTLV-I)-infected mature CD4 þ T-cells. To characterize the molecular modifications induced by HTLV-I infection, we compared HTLV-I-infected WE17/10 cells with control cells, using micro-arrays. Many calcium-related genes were progressively downmodulated over a period of 2 years. Infected cells acquired a profound decrease of intracellular calcium levels in response to ionomycin, timely correlated with decreased CD7 expression. Focusing on apoptosis-related genes and their relationship with CD7, we observed an underexpression of most antiapoptotic genes. Western blotting revealed increasing Akt and Bad phosphorylation, timely correlated with CD7 loss. This was shown to be phosphatidylinositol 3-kinase (PI3K)-dependent. Activation of PI3K/Akt induced resistance to the apoptotic effect of interleukin-2 deprivation. We thus propose the following model: HTLV-I infection induces a progressive decrease in CD3 genes expression, which eventually abrogates CD3 expression; loss of CD3 is known to perturb calcium transport. This perturbation correlates with loss of CD7 expression and induction of Akt and Bad phosphorylation via activation of PI3K. The activation of the Akt/Bad pathway generates a progressive resistance to apoptosis, at a time HTLV-I genes expression is silenced, thus avoiding immune surveillance. This could be a major event in the process of the malignant transformation into ATLL.

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Chemical Biology of the Sugar Code

et al. 2004

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A high-density coding system is essential to allow cells to communicate efficiently and swiftly through complex surface interactions. All the structural requirements for forming a wide array of signals with a system of minimal size are met by oligomers of carbohydrates. These molecules surpass amino acids and nucleotides by far in information-storing capacity and serve as ligands in biorecognition processes for the transfer of information. The results of work aiming to reveal the intricate ways in which oligosaccharide determinants of cellular glycoconjugates interact with tissue lectins and thereby trigger multifarious cellular responses (e.g. in adhesion or growth regulation) are teaching amazing lessons about the range of finely tuned activities involved. The ability of enzymes to generate an enormous diversity of biochemical signals is matched by receptor proteins (lectins), which are equally elaborate. The multiformity of lectins ensures accurate signal decoding and transmission. The exquisite refinement of both sides of the protein-carbohydrate recognition system turns the structural complexity of glycans--a demanding but essentially mastered problem for analytical chemistry--into a biochemical virtue. The emerging medical importance of protein-carbohydrate recognition, for example in combating infection and the spread of tumors or in targeting drugs, also explains why this interaction system is no longer below industrial radarscopes. Our review sketches the concept of the sugar code, with a solid description of the historical background. We also place emphasis on a distinctive feature of the code, that is, the potential of a carbohydrate ligand to adopt various defined shapes, each with its own particular ligand properties (differential conformer selection). Proper consideration of the structure and shape of the ligand enables us to envision the chemical design of potent binding partners for a target (in lectin-mediated drug delivery) or ways to block lectins of medical importance (in infection, tumor spread, or inflammation).

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

Cited by 101 publications

References 42 publications

Galectin-1–Mediated Apoptosis in Mycosis Fungoides: The Roles of CD7 and Cell Surface Glycosylation

Galectin-1–Mediated Apoptosis in Mycosis Fungoides: The Roles of CD7 and Cell Surface Glycosylation

HTLV-I infection of WE17/10 CD4+ cell line leads to progressive alteration of Ca2+ influx that eventually results in loss of CD7 expression and activation of an antiapoptotic pathway involving AKT and BAD which paves the way for malignant transformation

Chemical Biology of the Sugar Code

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