The ST3Gal-I Sialyltransferase Controls CD8+ T Lymphocyte Homeostasis by Modulating O-Glycan Biosynthesis

Priatel, John J.; Chui, Daniel; Hiraoka, Nobuyoshi; Simmons, Collan J.T; Richardson, Kevin B; Page, Dawne M.; Fukuda, Minoru; Varki, Nissi; Marth, Jamey D.

doi:10.1016/s1074-7613(00)80180-6

Cited by 279 publications

(272 citation statements)

References 51 publications

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“…Thus, the effects of the decrease in expression of ST6Gal I and increase in expression of ␣1-3GalT are amplified through their competition in the biosynthetic pathway. Conversely, in B cells, the ST6Gal I gene showed slightly increased expression (2), and the ␣1-3GalT gene showed a 3-fold decrease in RMA signal, the opposite from T cells. These results are consistent with the observed retention of N-linked glycans with the terminal NeuGc␣2-6Gal sequence in both resting and activated B cells (Fig.…”

Section: Glycan Transferase Changes Relevant To N-linked Glycansmentioning

confidence: 82%

“…In CD8 T cells, this glycosylation change reduces the affinity of CD8 for MHC class I, suggesting that sialylation of CD8 O-glycans modulates CD8 function during selection and maturation of CD8 T cells (5)(6)(7). Naive CD8 cells of ST3Gal I null mice that are constitutively PNA high undergo rapid apoptosis in the periphery, reducing the CD8 population to 10% of wild type (2). Yet, conversion from PNA low to PNA high is a natural consequence of activation of wild-type CD8 cells resulting from down-regulation of ST3Gal I (2,8,9).…”

Section: Activation Of Murine Cd4 ؉ and Cd8 ؉ T Lymphocytes Leads To mentioning

confidence: 99%

“…Naive CD8 cells of ST3Gal I null mice that are constitutively PNA high undergo rapid apoptosis in the periphery, reducing the CD8 population to 10% of wild type (2). Yet, conversion from PNA low to PNA high is a natural consequence of activation of wild-type CD8 cells resulting from down-regulation of ST3Gal I (2,8,9). In contrast, ST3Gal I is differentially regulated in activated and polarized Th1 and Th2 CD4 cells leading to the PNA high and PNA low phenotype, respectively (10).…”

Section: Activation Of Murine Cd4 ؉ and Cd8 ؉ T Lymphocytes Leads To mentioning

confidence: 99%

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Activation of Murine CD4+ and CD8+ T Lymphocytes Leads to Dramatic Remodeling ofN-Linked Glycans

Comelli¹,

Sutton-Smith

Qi³

et al. 2006

The Journal of Immunology

114

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Differentiation and activation of lymphocytes are documented to result in changes in glycosylation associated with biologically important consequences. In this report, we have systematically examined global changes in N-linked glycosylation following activation of murine CD4 T cells, CD8 T cells, and B cells by MALDI-TOF mass spectrometry profiling, and investigated the molecular basis for those changes by assessing alterations in the expression of glycan transferase genes. Surprisingly, the major change observed in activated CD4 and CD8 T cells was a dramatic reduction of sialylated biantennary N-glycans carrying the terminal NeuGcα2-6Gal sequence, and a corresponding increase in glycans carrying the Galα1-3Gal sequence. This change was accounted for by a decrease in the expression of the sialyltransferase ST6Gal I, and an increase in the expression of the galactosyltransferase, α1-3GalT. Conversely, in B cells no change in terminal sialylation of N-linked glycans was evident, and the expression of the same two glycosyltransferases was increased and decreased, respectively. The results have implications for differential recognition of activated and unactivated T cells by dendritic cells and B cells expressing glycan-binding proteins that recognize terminal sequences of N-linked glycans.

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Section: Glycan Transferase Changes Relevant To N-linked Glycansmentioning

confidence: 82%

Section: Activation Of Murine Cd4 ؉ and Cd8 ؉ T Lymphocytes Leads To mentioning

confidence: 99%

Section: Activation Of Murine Cd4 ؉ and Cd8 ؉ T Lymphocytes Leads To mentioning

confidence: 99%

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Activation of Murine CD4+ and CD8+ T Lymphocytes Leads to Dramatic Remodeling ofN-Linked Glycans

Comelli¹,

Sutton-Smith

Qi³

et al. 2006

The Journal of Immunology

114

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“…Sialylation of O-glycans by the ST3Gal I enzyme blocks PNA binding and also prevents the addition of polyLacNAc sequences to form core 2 O-glycans that bind galectin-1 and are required for galectin-1-induced T-cell death (41,42,49). For non-neoplastic human thymocytes and T cells, the ability to bind PNA correlates with susceptibility to galectin-1-induced death (20,21).…”

Section: Glycosylation Patterns In Mycosis Fungoides Lesionsmentioning

confidence: 99%

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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“…In support, hyposialylation of this marker induces apoptosis in T cells after cross-linking with the appropriate mAbs (29). Other authors working with the ST3-Gal-I sialyltransferase KO mice that contains CD43 undersialylated glycoforms have also postulated that the altered CD43 might interact in peripheral compartments with multivalent lectin-like molecules to induce CD8 T cell apoptosis (44). In this study, we postulate a sialylation-dependent checkpoint in the thymic compartment working on the DP thymocyte population in males.…”

Section: Discussionmentioning

confidence: 93%

A Sexual Dimorphism in Intrathymic Sialylation Survey Is Revealed by thetrans-Sialidase fromTrypanosoma cruzi

Mucci

Mocetti

Leguizamón

et al. 2005

The Journal of Immunology

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Sialylation is emerging as an important issue in developing thymocytes and is considered among the most significant cell surface modifications, although its physiologic relevance is far from being completely understood. It is regulated by the concerted expression of sialyl transferases along thymocyte development. After in vivo administration of trans-sialidase, a virulence factor from the American trypanosomatid Trypanosoma cruzi that directly transfers the sialyl residue among macromolecules, we found that the alteration of the sialylation pattern induces thymocyte apoptosis inside the “nurse cell complex.” This suggests a glycosylation survey in the development of the T cell compartment. In this study, we report that this thymocyte apoptosis mechanism requires the presence of androgens. No increment in apoptosis was recorded after trans-sialidase administration in females or in antiandrogen-treated, gonadectomized, or androgen receptor mutant male mice. The androgen receptor presence was required only in the thymic epithelial cells as determined by bone marrow chimeric mouse approaches. The presence of the CD43 surface mucin, a molecule with a still undefined function in thymocytes, was another absolute requirement. The trans-sialidase-induced apoptosis proceeds through the TNF-α receptor 1 deathly signaling leading to the activation of the caspase 3. Accordingly, the production of the cytokine was increased in thymocytes. The ability of males to delete thymocytes altered in their sialylation pattern reveals a sexual dimorphism in the glycosylation survey during the development of the T cell compartment that might be related to the known differences in the immune response among sexes.

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The ST3Gal-I Sialyltransferase Controls CD8+ T Lymphocyte Homeostasis by Modulating O-Glycan Biosynthesis

Cited by 279 publications

References 51 publications

Activation of Murine CD4+ and CD8+ T Lymphocytes Leads to Dramatic Remodeling ofN-Linked Glycans

Activation of Murine CD4+ and CD8+ T Lymphocytes Leads to Dramatic Remodeling ofN-Linked Glycans

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

A Sexual Dimorphism in Intrathymic Sialylation Survey Is Revealed by thetrans-Sialidase fromTrypanosoma cruzi

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