Analysis of lipid rafts in T cells

Thomas, Sunil; Preda-Pais, Anca; Casares, Sofía; Brumeanu, Teodor‐D.

doi:10.1016/j.molimm.2004.03.022

Cited by 68 publications

(47 citation statements)

References 93 publications

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“…Initial reports identified lipid rafts as detergent-insoluble membrane complexes that float in low-density gradient centrifugation (28,58,69). However, the observation that detergent can induce the formation of lipid rafts hampers these biochemical approaches (70,71).…”

Section: Discussionmentioning

confidence: 99%

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Differential Regulation of GM1 and Asialo-GM1 Expression by T Cells and Natural Killer (NK) Cells in Respiratory Syncytial Virus Infection

et al. 2008

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We previously reported that respiratory syncytial virus (RSV) infection increases lung CD8 ϩ T cell GM1 expression. The related lipid asialo-GM1 (ASGM1) is expressed by T cells in viral infection and by natural killer (NK) cells. The in vivo co-expression of GM1 and ASGM1 by immune cells is not defined. Here we analyzed lung lymphocyte GM1 and ASGM1 expression in RSV-infected mice. GM1 and ASGM1 were coordinately upregulated by activated CD8 ϩ T cells in RSV-infected BALB/c and C57BL/6 mice. In contrast, RSV infection had no effect on constitutively high NK cell GM1 expression, while increasing NK cell ASGM1 expression. GM1 and ASGM1 co-localized in lipid raft structures in NK and CD8 ϩ T cells sorted from the lungs of RSV-infected mice. Anti-ASGM1 Ab treatment of RSV-infected BALB/c mice depleted GM1/ASGM1-expressing NK cells and GM1/ASGM1-expressing T cells, reduced lung IFN-␥ levels, increased viral load, delayed viral clearance, and reduced illness. STAT1 Ϫ/Ϫ mice are more susceptible to RSV replication and disease than wild-type mice. In RSV-infected STAT1 Ϫ/Ϫ mice, anti-ASGM1 Ab altered cytokine levels, but in contrast to BALB/c mice, antibody treatment had no effect on viral load or illness. Taken together, GM1 and ASGM1 expression are differentially regulated by T and NK cells in RSV infection. Also, GM1/ASGM1-expressing cells are important for control of RSV in BALB/c mice, whereas STAT1 Ϫ/Ϫ mice clear RSV by an alternative pathway. 327

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Section: Discussionmentioning

confidence: 99%

“…(56). GM1 and ASGM1 are GSLs associated with lipid rafts and cell activation (30,33,58,59). We hypothesized in the current study that ASGM1 and GM1 are coordinately expressed on NK and CD8 ϩ T cells in RSV infection.…”

Section: Effect Of Rsv Infection On Nk and Cd8 ϩ T Cell Asgm1 And Gm1mentioning

confidence: 99%

Differential Regulation of GM1 and Asialo-GM1 Expression by T Cells and Natural Killer (NK) Cells in Respiratory Syncytial Virus Infection

et al. 2008

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“…The alteration of lipid rafts after T cell activation has been demonstrated extensively. Following activation by cross-linking of various receptors on T cells, the microdomains of lipid rafts become larger and more stable than those in resting T cells, often being attached to the cytoskeleton [26,27]. Lipid rafts play a critical role in the maturation, activation and immunological synapse formation in CD4 + and CD8…”

Section: D4d8mentioning

confidence: 99%

β-Glucosylceramide ameliorates liver inflammation in murine autoimmune cholangitis

Zhang

Moritoki

Tsuneyama

et al. 2009

Clinical and Experimental Immunology

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SummaryWe have demonstrated spontaneous development of autoimmune cholangitis, similar to human primary biliary cirrhosis, in mice expressing a dominant negative form of the transforming growth factor-b receptor (dnTGFbRII) restricted to T cells. The autoimmune cholangitis appears to be mediated by autoreactive CD8 + T lymphocytes that home to the portal tracts and biliary system. Because the liver pathology is primarily secondary to CD8+ T cells, we have determined herein whether administration of b-glucosylceramide (GC), a naturally occurring plant glycosphingolipid, alters the natural history of disease in this model. We chose GC because previous work has demonstrated its ability to alter CD8 + T cell responses and to down-regulate tissue inflammation. Accordingly, dnTGF-bRII mice were treated with either GC or control for a period of 18 weeks beginning at 6 weeks of age. Importantly, in mice that received GC, there was a significant decrease in the frequency and absolute number of autoreactive liverinfiltrating CD8 + T cells, accompanied by a significant decrease in activated CD44 high CD8 + T cell populations. Further, there was a significant reduction in portal inflammation in GC-treated mice. Interestingly, there were no changes in anti-mitochondrial antibodies, CD4 + T cells, CD19 + B cells or natural killer (NK) T cell populations, indicating further that the beneficial effects of GC on liver inflammation were targeted specifically to liverinfiltrating CD8 + T cells. These data suggest that further work on GC in models of CD8 + T-mediated inflammation are needed and point to a new therapeutic venue for potentially treating and/or modulating autoimmune disease.

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“…The sialoglycosphingolipid GM1 is the most commonly used marker of lipid rafts, and GM1 accumulates in the immunological synapse (4). In motile T cells, GM1 accumulates in the rear of the cell whereas GM3 accumulates in the leading edge (5).…”

mentioning

confidence: 99%

Cutting Edge: Oseltamivir Decreases T Cell GM1 Expression and Inhibits Clearance of Respiratory Syncytial Virus: Potential Role of Endogenous Sialidase in Antiviral Immunity

Moore¹,

Michael²,

Zhou³

et al. 2007

The Journal of Immunology

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The sialoglycosphingolipid GM1 is important for lipid rafts and immune cell signaling. T cell activation in vitro increases GM1 expression and increases endogenous sialidase activity. GM1 expression has been hypothesized to be regulated by endogenous sialidase. We tested this hypothesis in vivo using a mouse model of respiratory syncytial virus (RSV) infection. RSV infection increased endogenous sialidase activity in lung mononuclear cells. RSV infection increased lung CD8+ T cell surface GM1 expression. Activated CD8+ T cells in the lungs of RSV-infected mice were GM1high. Treatment of RSV-infected mice with the sialidase/neuraminidase inhibitor oseltamivir decreased T cell surface GM1 levels. Oseltamivir treatment decreased RSV-induced weight loss and inhibited RSV clearance. Our data indicate a novel role for an endogenous sialidase in regulating T cell GM1 expression and antiviral immunity. Also, oseltamivir, an important anti-influenza drug, inhibits the clearance of a respiratory virus that lacks a neuraminidase gene, RSV.

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Analysis of lipid rafts in T cells

Cited by 68 publications

References 93 publications

Differential Regulation of GM1 and Asialo-GM1 Expression by T Cells and Natural Killer (NK) Cells in Respiratory Syncytial Virus Infection

Differential Regulation of GM1 and Asialo-GM1 Expression by T Cells and Natural Killer (NK) Cells in Respiratory Syncytial Virus Infection

β-Glucosylceramide ameliorates liver inflammation in murine autoimmune cholangitis

Cutting Edge: Oseltamivir Decreases T Cell GM1 Expression and Inhibits Clearance of Respiratory Syncytial Virus: Potential Role of Endogenous Sialidase in Antiviral Immunity

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