Cutting Edge: CD7 Delivers a Pro-Apoptotic Signal During Galectin-1-Induced T Cell Death

Pace, Karen E.; Hahn, Hejin P.; Pang, Mabel; Nguyen, Julie T.; Baum, Linda G.

doi:10.4049/jimmunol.165.5.2331

Cited by 203 publications

(181 citation statements)

References 37 publications

(38 reference statements)

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“…It was reported that CD7 delivers a proapoptotic signal during galectin-1-induced T-cell death. 10 Furthermore, CD4 þ CD7 À leukemic T cells from patients with Sezary syndrome are protected from galectin-1-triggered T-cell death. 11 It has also been shown that survival of acute myeloid leukemia cells requires phosphatidylinositol 3-kinase (PI3K) activation.…”

Section: Introductionmentioning

confidence: 99%

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

Akl

Badran

Zein³

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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Section: Introductionmentioning

confidence: 99%

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

Akl

Badran

Zein³

et al. 2007

Leukemia

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“…We have previously demonstrated reversal of galectin-1 resistance in the CD7 Ϫ Sezary cell line Hut78 by expressing CD7 in these cells (36). This implied that all other components of the galectin-1 death pathway besides CD7 were present in Hut78 cells.…”

Section: Discussionmentioning

confidence: 94%

“…1B) indicates that Sezary cells are exposed to galectin-1 in vivo. We hypothesized that Sezary cells may resist galectin-1-mediated apoptosis either because the malignant cells do not express CD7 that is essential for galectin-1-mediated apoptosis (36) or because PNA Ϫ Sezary cells have aberrant cell surface glycosylation that contributes to decreased galectin-1 sensitivity. To examine the relationship between CD7 expression, cell surface glycosylation, and susceptibility to galectin-1, we analyzed cell surface glycosylation and CD7 expression of four Sezary cell lines, Hut78, MyLa 2059, HH, and SeAx/i.…”

Section: Cell Surface Phenotype Of Sezary Cell Linesmentioning

confidence: 99%

“…CD7 is a T-cell surface glycoprotein that binds galectin-1 and is essential for galectin-1-mediated T-cell death (36,37). 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).…”

mentioning

confidence: 99%

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

et al. 2003

Self Cite

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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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“…Interestingly, we found that another human T cell line, HuT-78, was totally resistant to Tet-mediated cytotoxicity (unpublished observations). The HuT-78 T cell line has many characteristics that differ from those of other commonly used T cell lines, such as much lower expression of CD2, CD4, and CD45 as well as much higher resistance to anti-Fas-and TNF-␣-mediated cell death (34,35). The signaling pathway that mediates Tet-induced cytotoxicity may be altered in this particular cell line.…”

Section: Tet-induced Cell Death Appeared To Be Highly Specific Towardmentioning

confidence: 99%

Western and Chinese Antirheumatic Drug-Induced T Cell Apoptotic DNA Damage Uses Different Caspase Cascades and Is Independent of Fas/Fas Ligand Interaction

Lai

Chang

et al. 2001

The Journal of Immunology

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Spontaneous or therapeutic induction of T cell apoptosis plays a critical role in establishing transplantation tolerance and maintaining remission of autoimmune diseases. We investigated the mechanisms of apoptosis induced by Chinese and Western antirheumatic drugs (ARDs) in human T cells. We found that hydroxychloroquine, Tripterygium wilfordii hook F, and tetrandrine (Tet), but not methotrexate, at therapeutic concentrations can cause T cell death. In addition, Tet selectively killed T cells, especially activated T cells. Although ARD-induced cytotoxicity was mediated through apoptotic mechanisms, Fas/Fas ligand interaction was not required. We further demonstrated that the processes of phosphatidylserine externalization and DNA damage along the ARD-induced T cell apoptotic pathway could operate independently, and that selective inhibition of DNA damage by caspase inhibitors did not prevent T cells from undergoing cell death. Moreover, we found that Tet- and Tripterygium wilfordii hook F-induced T cell DNA damage required caspase-3 activity, and hydroxychloroquine-induced T cell DNA damage was mediated through a caspase-3- and caspase-8-independent, but Z-Asp-Glu-Val-Asp-fluomethyl ketone-sensitive, signaling pathway. Finally, the observation that ARD-induced activation of caspase-3 in both Fas-sensitive and Fas-resistant Jurkat T cells indicates that Fas/Fas ligand interaction plays no role in ARD-induced T cell apoptosis. Our observations provide new information about the complex apoptotic mechanisms of ARDs, and have implications for combining Western and Chinese ARDs that have different immunomodulatory mechanisms in the therapy of autoimmune diseases and transplantation rejection.

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Cutting Edge: CD7 Delivers a Pro-Apoptotic Signal During Galectin-1-Induced T Cell Death

Cited by 203 publications

References 37 publications

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

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

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

Western and Chinese Antirheumatic Drug-Induced T Cell Apoptotic DNA Damage Uses Different Caspase Cascades and Is Independent of Fas/Fas Ligand Interaction

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