HIV‐1 down‐regulates the expression of CD1d via Nef

Chen, Nan; McCarthy, Corinna; Drakesmith, Hal; Li, Demin; Cerundolo, Vincenzo; McMichael, Andrew J.; Screaton, Gavin; Xu, Xiao-Ning

doi:10.1002/eji.200535487

Cited by 117 publications

(106 citation statements)

References 23 publications

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“…36,37 The HTLV-1 proviral load was significantly higher in DCs from HAM/TSP patients than from ACs (Figure 4). To determine the effect of HTLV-1 on CD1d expression and DC activation, we statistically analyzed the correlation between the proviral load in DCs and the expression level of CD1d and DC-activation markers.…”

Section: Discussionmentioning

confidence: 99%

“…35 Moreover, human immunodeficiency virus type 1 (HIV-1) reportedly down-regulates CD1d expression. 36,37 We hypothesized that HTLV-1 infection of DCs may alter their function by affecting the expression level of CD1d, CD86, and HLA-ABC on the cell surface. Therefore, we first separated mDCs and pDCs from 5 ACs and 5 HAM/TSP patients by fluorescence-activated cell sorter (FACS) and quantified the HTLV-1 proviral load.…”

Section: Equivalent Expression Level Of Cd1d In All Study Groupsmentioning

confidence: 99%

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Severe loss of invariant NKT cells exhibiting anti–HTLV-1 activity in patients with HTLV-1–associated disorders

Azakami

Sato

Araya

et al. 2009

Blood

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Invariant natural killer T (iNKT) cells are unique T cells that regulate the immune response to microbes, cancers, and autoimmunity. We assessed the characteristics of iNKT cells from persons infected with human T-lymphotropic virus type 1 (HTLV-1). Whereas most infected persons remain asymptomatic carriers (ACs IntroductionHuman T-cell lymphotropic virus type 1 (HTLV-1) causes persistent infection. Whereas most infected persons remain asymptomatic carriers (ACs), 3% to 5% develop a T-cell malignancy termed adult T-cell leukemia (ATL), and another 0.25% to 3% develop a chronic progressive inflammatory neurologic disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/ TSP). [1][2][3] One of the most important pathogenic factors in HAM/ TSP is an increased HTLV-1 load in the peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid, 4-6 which suggests that in affected persons, virus control is inadequate. A higher HTLV-1 load increases the risk of HAM/TSP and ATL. 4,7 Therefore, the precise mechanisms controlling HTLV-1-infected cells must be better understood. With regard to the host defense mechanisms involved in HTLV-1 infection, the role of HTLV-1-specific CD8 ϩ cytotoxic T lymphocytes (CTLs) has been studied. [8][9][10] The HTLV-1-specific CTL response is critical for a low viral load to be maintained. [9][10][11] Despite the high frequency of HTLV-1-specific CTLs, the number of HTLV-1-infected T cells is surprisingly high in HAM/TSP patients. 5,6 We and others have reported that the maturation and functioning of HTLV-1-specific CTLs are inadequate in HAM/TSP patients, although in vitro studies have shown that these CTLs exert cytolytic activity against HTLV-1-expressing target cells. 12,13 Therefore, we hypothesize that there may be another cell population without CTLs that contributes to the control of HTLV-1-infected T cells.A unique T-cell subpopulation, natural killer T (NKT) cells, constitute a subset of lymphocytes that share the features of both innate and adaptive immune cells. Unlike conventional T cells, NKT cells express a T-cell receptor (TCR) that recognizes glycolipids instead of protein antigens. Moreover, these cells share properties and receptors with NK cells. They rapidly produce granzymes and perforins on stimulation. Among the CD3 ϩ T cells in human blood, 10% to 25% express NK cell-surface molecules, such as CD161, and these can be classified as NKT cells. 14,15 A small population of T cells within this NKT cell subset expresses a highly conserved V␣24J␣18 TCR chain that associates preferentially with V␤11. [16][17][18] These T cells are referred to as invariant NKT (iNKT) cells. Very recently, a novel clonotypic monoclonal antibody 6B11 specific for the V␣24J␣18 TCR chain has been shown to selectively stain human iNKT cells. 18,19 Activation of human iNKT cells requires the presentation of glycolipids, such as ␣-galactosylceramide (␣-GalCer) on the major histocompatibility complex class I-like molecule CD1d. 20 ␣-GalCer stimulation induces rapid cytoki...

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Section: Discussionmentioning

confidence: 99%

Section: Equivalent Expression Level Of Cd1d In All Study Groupsmentioning

confidence: 99%

Severe loss of invariant NKT cells exhibiting anti–HTLV-1 activity in patients with HTLV-1–associated disorders

Azakami

Sato

Araya

et al. 2009

Blood

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“…TGN has also been found to be associated with Nef mediated downregulation of non classical MHC-I like CD1d molecule that has been demonstrated by retention of CD1d in TGN and internalization from the cell surface [25]. In another study, it has also been demonstrated that a KSHV induces internalization of MHC-I complex by endocytosis and subsequently redirects them to TGN and targets MHC-I to the lysosomal compartment.…”

Section: Regulation Of Trans-golgi Network (Tgn)mentioning

confidence: 85%

Immune Regulation and Evasion of Mammalian Host Cell Immunity During Viral Infection

et al. 2013

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The mammalian host immune system has wide array of defence mechanisms against viral infections. Depending on host immunity and the extent of viral persistence, either the host immune cells might clear/restrict the viral load and disease progression or the virus might evade host immunity by down regulating host immune effector response(s). Viral antigen processing and presentation in the host cells through major histocompatibility complex (MHC) elicit subsequent anti-viral effector T cell response(s). However, modulation of such response(s) might generate one of the important viral immune evasion strategies. Viral peptides are mostly generated by proteolytic cleavage in the cytosol of the infected host cells. CD8 ? T lymphocytes play critical role in the detection of viral infection by recognizing these peptides displayed at the plasma membrane by MHC-I molecules. The present review summarises the current knowledge on the regulation of mammalian host innate and adaptive immune components, which are operative in defence mechanisms against viral infections and the variety of strategies that viruses have evolved to escape host cell immunity. The understanding of viral immune evasion strategies is important for designing anti-viral immunotherapies.

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“…Moreover, such a model could explain the recent observation that viral pathogens, including HSV1, have evolved mechanisms to subvert CD1d antigen presentation [28][29][30][31][32][33]. Future studies will reveal more insight into the intriguing interplay between viruses and the CD1 antigen presentation system and the ligands recognized by NKT cells in the context of virus infection.…”

Section: Discussionmentioning

confidence: 97%

“…These [18,25] or improves disease outcome [12,26]. Moreover, viruses subvert antigen presentation through CD1d [27][28][29][30][31][32][33], indicating its importance in antiviral immune defense.The mechanisms leading to activation of CD1d-restricted NKT cells in humans infected with viral pathogens are unknown. However, DC will play an important role as they link the innate and adaptive antiviral immunity [34].…”

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confidence: 99%

Viral danger signals control CD1d de novo synthesis and NKT cell activation

et al. 2008

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The nonpolymorphic CD1 molecules present lipid antigens to T cells. In myeloid DC humans express five different CD1 proteins (CD1a-e; the corresponding CD1 genes are designated CD1A-E). A role for CD1d-restricted NKT cells in the control of virus infections has been delineated from clinical observations, mouse models and viral evasion mechanisms targeting CD1d. How NKT cells are activated by virus infections is unclear. We found that human myeloid DC differentially regulate CD1 antigen presentation in response to viral danger signals. Stimulation with type I IFN, viral TLR ligands or viruses strongly enhanced the number of CD1D transcripts in human myeloid DC but diminished the abundance of CD1A, CD1B and CD1E mRNA. These changes on the transcriptional level were mirrored by altered cellular distribution and increased surface expression of CD1d. As a consequence NKT cells were activated and showed a Th1-like response. Moreover, NKT cell activation in PBMC exposed to viral danger signals was dependent on human plasmacytoid DC which produce large amounts of IFN-a. In conclusion, our data indicate that viral danger signals trigger NKT cell activation by enhancing CD1d de novo synthesis through increasing the abundance of CD1D mRNA in human myeloid DC. IntroductionThe immune system detects viruses by recognizing antigens loaded on specialized surface molecules. The highly polymorphic MHC molecules bind to diverse peptides, traffic to the cell surface, and display this information to T cells [1]. Although distantly related to MHC proteins, the nonpolymorphic CD1 proteins constitute an evolutionarily distinct family of antigenpresenting molecules [2]. Humans express five different CD1 proteins (CD1a-e; the corresponding CD1 genes are designated CD1A-E). They are further divided into group 1 (CD1a-c) and group 2, which contains CD1d as the sole member. In contrast, CD1e is not expressed on the cell surface and is an intermediate form in terms of its homology to the other CD1 molecules. Accordingly, it is regarded as a group 3 CD1 molecule [3].By trafficking through endosomal compartments, CD1 proteins pick up antigens in a similar fashion to MHC class II molecules [4]. However, instead of peptides, CD1 molecules present lipids, glycolipids or lipopeptides of either foreign or self origin [2,5]. The CD1d-restricted NKT cells can also recognize a-galactosylceramide (aGalCer), a well-studied and highly potent CD1d ligand derived from a marine sponge [6,7]. These [18,25] or improves disease outcome [12,26]. Moreover, viruses subvert antigen presentation through CD1d [27][28][29][30][31][32][33], indicating its importance in antiviral immune defense.The mechanisms leading to activation of CD1d-restricted NKT cells in humans infected with viral pathogens are unknown. However, DC will play an important role as they link the innate and adaptive antiviral immunity [34]. DC sense invading viruses by detecting conserved pathogen-associated molecular patterns through a variety of different pattern recognition receptors, e.g. TLR...

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HIV‐1 down‐regulates the expression of CD1d via Nef

Cited by 117 publications

References 23 publications

Severe loss of invariant NKT cells exhibiting anti–HTLV-1 activity in patients with HTLV-1–associated disorders

Severe loss of invariant NKT cells exhibiting anti–HTLV-1 activity in patients with HTLV-1–associated disorders

Immune Regulation and Evasion of Mammalian Host Cell Immunity During Viral Infection

Viral danger signals control CD1d de novo synthesis and NKT cell activation

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