Selective Loss of Natural Killer T Cells by Apoptosis following Infection with Lymphocytic Choriomeningitis Virus

Hobbs, Jacqueline A.; Cho, Sungyoo; Roberts, Tonya; Sriram, Venkataraman; Zhang, Jianhua; Xu, Ming; Brutkiewicz, Randy R.

doi:10.1128/jvi.75.22.10746-10754.2001

Cited by 97 publications

(118 citation statements)

References 71 publications

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“…In brief, lipids resuspended in PBS (pH 7.4) were mixed with the dimers and incubated at 37 C overnight. Mouse liver mononuclear cells, isolated as described previously [48], were treated with 2.4G2 hybridoma supernatant before staining for cytofluorography with empty or lipid-loaded CD1d dimers, FITC-conjugated anti-mouse-TCRb and biotinylated anti-NK1.1 (Pharmingen). The dimers were directly labeled with phycoerythrin using a mouse IgG 1 -specific Zenon labeling kit following the instructions of the manufacturer (Molecular Probes, Eugene, OR, USA).…”

Section: Cd1d-ig Dimer Staining Of Nkt Cellsmentioning

confidence: 99%

Cell wall glycosphingolipids ofSphingomonas paucimobilisare CD1d-specific ligands for NKT cells

et al. 2005

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The current consensus on characterization of NKT cells is based on their reactivity to the synthetic glycolipid, a-galactosylceramide (a-GalCer) in a CD1d-dependent manner. Because of the limited availability of a-GalCer, there is a constant search for CD1d-presented ligands that activate NKT cells. The a-anomericity of the carbohydrate is considered to be an important requisite for the CD1d-specific activation of NKT cells. The gram-negative, lipopolysaccharide-free bacterium Sphingomonas paucimobilis is known to contain glycosphingolipids (GSL) with a-anomeric sugars attached to the lipid chain. Here, we report that GSL extracted from this bacterium are able to stimulate NKT cells in a CD1d-specific manner. In addition, soluble CD1d-Ig dimers loaded with this lipid extract specifically bind to NKT cells (but not conventional T cells). Further studies on the S. paucimobilis GSL could potentially lead to other natural sources of CD1d-specific ligands useful for NKT cell analyses and aimed at identifying novel therapies for a variety of disease states. IntroductionLipid antigens, including phospholipids and glycosphingolipids (GSL), are presented by CD1d -a subset of the CD1 family of MHC class I-like molecules -to specialized immune effector cells called NKT cells [1]. Located on a different chromosome than the MHC, five different CD1 genes encode CD1 molecules -CD1a, CD1b, CD1c, CD1d and CD1e -in humans, whereas only two homologues of CD1d (CD1d1 and CD1d2) are present in mice [2]. On the basis of the crystal structure of mouse CD1d1 [3], it is predicted that the fatty-acyl chains are buried in the hydrophobic pocket of the molecule with the hydrophilic head-group of the lipid antigen available outside the molecule for its interaction with the NKT cell receptor. Even though the lipidbinding groove of CD1d is widely accommodative of many lipid groups, it is believed that only the sugar structures in a-anomeric orientation are able to stimulate NKT cells [4]. Because of the lack of physiological glycolipids with terminal a-anomeric sugars, it is hypothesized that both altered selfglycolipids during a pathological process and exogenous antigenic glycolipids could be potential ligands presented by CD1d [4]. The presence of GSL in the cell wall of some bacterial strains indicates the possibility of these bacterial GSL being presented by CD1d. Although human CD1a, b and c molecules are known to present mycobacterial antigens to human NKT cells, there is a lack of substantial evidence to show that CD1d has the ability to present these microbial lipids [5]. In a recent study, Fischer et al. [6] were able to show that mycobacterial phosphoinositolmannosides (PIM) could bind to soluble CD1d and activate human and mouse NKT cells. However, only a fraction of NKT cells detected by agalactosylceramide (a-GalCer) could be stained by a CD1d tetramer loaded with mycobacterial PIM [6]. A recent study [7] was able to show the binding of synthetic a-GalNAc containing GSL to cell surface CD1d, but no functional studies were done t...

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Section: Cd1d-ig Dimer Staining Of Nkt Cellsmentioning

confidence: 99%

Cell wall glycosphingolipids ofSphingomonas paucimobilisare CD1d-specific ligands for NKT cells

et al. 2005

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“…Splenocyte, liver MNC, and PEC isolation was described previously [28]. Peripheral blood was collected from euthanized mice via cardiac puncture and treated with 0.5 mM EDTA and stained with the appropriate mAb.…”

Section: Organ Isolationmentioning

confidence: 99%

Myeloid marker expression on antiviral CD8⁺ T cells following an acute virus infection

et al. 2003

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CD11b, CD11c, and F4/80 are normally used to define dendritic cell and/or macrophage populations. In this study, the expression of all three markers was observed on CD8 + T cells following infection of mice with several distinct viruses. Using lymphocytic choriomeningitis virus as a model virus, it was found that relatively more CD11b + CD8 + and CD11c + CD8 + T cells were present in the periphery than in primary lymphoid organs; in contrast, the F4/ 80 + CD8 + T cell population was more prevalent in the spleen. All three myeloid markers were detected on virus-specific CTL. The expression of CD11b and CD11c on CD8 + T cells correlated with their level of CTL activity, whereas the F4/80 + CD8 + T cell population increased after the peak of the CTL response but did not have higher CTL activity. These data suggest that there is a differential induction of CD11b, CD11c, and F4/80 on virus-specific CD8 + T cells following an acute virus infection.

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“…The role for NKT cells in the pathogenesis of infectious diseases is less clear. However, the CD4 + V § 24 NKT cells were recently found to be extremely sensitive to HIV infection [11,23,24], and the corresponding murine V § 14 NKT cells are lost during acute infection with lymphocytic choriomeningitis virus (LCMV) [25].…”

Section: Introductionmentioning

confidence: 99%

Dominant effector memory characteristics, capacity for dynamic adaptive expansion, and sex bias in the innate Vα24 NKT cell compartment

2003

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V § 24 natural killer T (NKT) cells are innate immune cells that recognize self and nonself glycolipids presented by CD1d molecules, and play immunoregulatory roles in autoimmunity and tumor immunity. We have investigated the circulating V § 24 NKT cells in a large cohort of human subjects. CCR7 -CD45RO + effector memory cells dominated both CD4 + and CD4 -NKT subsets, while a minority displayed a central memory phenotype. CD4 -central memory NKT cells, however, were atypical in that they largely lacked CD62L expression. Overall, CD4 -NKT cells displayed a functional phenotype with effector characteristics, while the CD4 + subset appeared immunoregulatory. Interestingly, NKT cell numbers in blood varied widely between subjects, and elevated numbers of these cells were much more common in women than in men. The CD4 + subset dominated the NKT cell compartment in both sexes, while circulating NKT cell numbers above 0.1% were associated with an expanded CD4 -subset. Although NKT cell numbers were generally stable over time, we describe a dynamic fivefold expansion that was associated with a skewing of the NKT CD4 + :CD4 -ratio that persisted after numbers returned to base line. Thus, the two NKT cell subsets display different properties and dynamics that will influence their function as innate immunoregulatory and effector cells.

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Selective Loss of Natural Killer T Cells by Apoptosis following Infection with Lymphocytic Choriomeningitis Virus

Cited by 97 publications

References 71 publications

Cell wall glycosphingolipids ofSphingomonas paucimobilisare CD1d-specific ligands for NKT cells

Cell wall glycosphingolipids ofSphingomonas paucimobilisare CD1d-specific ligands for NKT cells

Myeloid marker expression on antiviral CD8⁺ T cells following an acute virus infection

Dominant effector memory characteristics, capacity for dynamic adaptive expansion, and sex bias in the innate Vα24 NKT cell compartment

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Selective Loss of Natural Killer T Cells by Apoptosis following Infection with Lymphocytic Choriomeningitis Virus

Cited by 97 publications

References 71 publications

Cell wall glycosphingolipids ofSphingomonas paucimobilisare CD1d-specific ligands for NKT cells

Cell wall glycosphingolipids ofSphingomonas paucimobilisare CD1d-specific ligands for NKT cells

Myeloid marker expression on antiviral CD8+ T cells following an acute virus infection

Dominant effector memory characteristics, capacity for dynamic adaptive expansion, and sex bias in the innate Vα24 NKT cell compartment

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Myeloid marker expression on antiviral CD8⁺ T cells following an acute virus infection