The CD160+ CD8high cytotoxic T cell subset correlates with response to HAART in HIV-1+ patients

Nikolova, Maria; Muhtarova, Maria; Taskov, Hristo; Kostov, K.; Vezenkov, L.; Mihova, Antoaneta; Boumsell, Laurence; Bensussan, Armand

doi:10.1016/j.cellimm.2005.01.012

Cited by 23 publications

(25 citation statements)

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“…This exhausted state is associated with the upregulation of multiple activation and coinhibitory molecules (see below) (49)(50)(51)(52)(53)(54)(55). Several studies have demonstrated that prolonged ARV therapy results in some restoration of polyfunctionality and at least partial downregulation of activation and exhaustion markers (49)(50)(51)(52)(56)(57)(58)(59)(60). It is tempting to speculate that, despite being reduced in numbers, the HIV-specific CD8 + T cells that remain in ARV-treated subjects may be more functional, less restrained by coinhibition, and less proapoptotic.…”

Section: + T Cell-mediated Eradicationmentioning

confidence: 99%

“…Coinhibitory receptors, including PD-1, TIM-3, CD160, 2B4, LAG-3, and CTLA-4, play a critical role in the maintenance of exhaustion (49)(50)(51)(52)(53)(54)(55). Blockade of these receptorseither alone or in combination -has enhanced T cell function in vitro and viral control in multiple animal models (49)(50)(51)(52)(53)(54)(55)(129)(130)(131)(132), providing a rationale for testing coinhibitory pathway blockade as an immunotherapeutic strategy in HIV infection. Additional enthusiasm for this approach can be drawn from advances in cancer immunotherapy, in which Abs that block the PD-1 and CTLA-4 pathways have been highly successful and are considered breakthrough drugs in the treatment of solid tumors (133).…”

Section: Cd8 + T Cell Compartmentalization and The Viral Reservoirmentioning

confidence: 99%

“…HIV-specific CD8 + T cell efficacy is partly limited by the effects of chronic immune stimulation on CD8 + T cell function. A variety of coinhibitory molecules, including programmed death 1 (PD-1), T cell Ig and mucin domain 3 (TIM-3), CD160, the NK cell receptor 2B4, lymphocyte activation gene 3 (LAG-3), and cytotoxic T lymphocyte antigen 4 (CTLA-4), which impair the antiviral function of HIV-specific CD8 + T cells that negatively regulate immune function, are expressed under conditions of chronic antigenic stimulation (49)(50)(51)(52)(53)(54)(55). Simultaneous expression of multiple coinhibitory molecules may result in even more profound functional immune impairment (71).…”

Section: + T Cell-mediated Eradicationmentioning

confidence: 99%

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HIV-specific CD8+ T cells and HIV eradication

Jones¹,

Walker²

2016

Journal of Clinical Investigation

111

106

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Section: + T Cell-mediated Eradicationmentioning

confidence: 99%

Section: Cd8 + T Cell Compartmentalization and The Viral Reservoirmentioning

confidence: 99%

Section: + T Cell-mediated Eradicationmentioning

confidence: 99%

See 1 more Smart Citation

HIV-specific CD8+ T cells and HIV eradication

Jones¹,

Walker²

2016

Journal of Clinical Investigation

111

106

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“…CD160 expression is restricted to the cytotoxic CD56 dim NK lymphocyte subset (18 -20) and to circulating CD8 ϩ T cells expressing granzyme B and perforin (21). We previously established that the engagement of CD160 receptors at the cell surface leads to the production of cytokines and the induction of cytotoxic functions (22,23).…”

Section: N Atural Killer Cells Are a Class Of Lymphocytes Involved Inmentioning

confidence: 99%

A Soluble Form of the MHC Class I-Specific CD160 Receptor Is Released from Human Activated NK Lymphocytes and Inhibits Cell-Mediated Cytotoxicity

Giustiniani

Marie‐Cardine

Bensussan

2007

The Journal of Immunology

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CD160 is a GPI-anchored lymphocyte surface receptor in which expression is mostly restricted to the highly cytotoxic CD56dimCD16+ peripheral blood NK subset. We previously reported that MHC class I (MHC-I) molecules bind to CD160 receptors on circulating NK lymphocytes and that this interaction triggers their cytotoxic activity and cytokine production. We also observed that CD160 surface expression on NK cells is down-modulated upon activation with PMA or IL-2. In this study, we further report that short-time incubation of NK lymphocytes with IL-15 converts the membrane-bound CD160 to a soluble form through a proteolytic cleavage involving a metalloprotease. Thus, CD160 is no longer detected at the cell surface, but can be immunoprecipitated from the NK cell culture medium. Interestingly, CD160 transcript remains highly expressed during the process of protein shedding. In addition, we demonstrate that CD160 mRNA synthesis can be induced in CD56bright separated lymphocytes following exposure to IL-15. By producing a Flag-tagged soluble CD160 protein, we establish that its binding to MHC-I molecules results in the inhibition of the cytotoxic CD8+ T lymphocyte activity and of the CD160-mediated NK cell cytotoxicity. Thus, we show that activated NK lymphocytes release a soluble form of CD160 that functionally impairs the MHC-I-specific cytotoxic CD8+ T lymphocyte responsiveness.

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“…This soluble CD160 impaired NK activation, possibly by competing for binding to MHC-I molecules. CD160 was not only found to be expressed on NK cells but it was also detected at the surface of CD8 T cells [5,6], a minor subset of circulating CD4 T cells [7], cutaneous T cells [8,9], γδ T lymphocytes, intestinal intraepithelial T cells, activated endothelial cells [10], and mast cells [11]. Of note, whereas human B cells lack CD160 expression, B-cell chronic lymphocytic leukaemia (CLL) expresses CD160 both at the protein and mRNA level [12].…”

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confidence: 99%

CD160: A Multifunctional Cell Surface Receptor

Bensussan¹

2014

MOJI

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Submit Manuscript | http://medcraveonline.com of co-regulatory signals. Besides, as CD160 expression appears tightly regulated in lymphocytes, analysis of the mechanisms controlling gene expression were of interest. CD160 have been clone on human chromosome 1 [16]. Analysis of its promoter region identified several conserved transcription binding sites in its minimal promoter region. Among these the AML1/RUNX1 transcriptional regulator was shown to be essential for CD160 expression [17]. RUNX family proteins play an important role in the NK cell differentiation [18].For example, AML-2 was identified as the predominant KIR binding factor controlling clonally expressed KIR genes during NK cell development [19] and AML-1 participates to the transcriptional control of important genes implicated in cytotoxicity such as IL2, 21]. Like in NK cells where CD160 is present at the surface of CD56dim, CD160 expression is fairly well associated with cytotoxic T or effector-memory lymphocytes. In the skin a resident CD4+ effector-memory T cell population, representing about 30 % of the cutaneous CD4+ T cells have been identified that express CD160 and skin addressing molecules such as CLA and CCR4 [9]. These cells have a cytotoxic potential and are probably important for skin immunosurveillance but the precise regulatory role of CD160 in this context is still unknown.On the other hand CD160 expression has been shown on growing, but not quiescent endothelial cells [10]. Here CD160 was clearly an inhibitory receptor as its cross-linking lead to an antiangiogenic effect in several model of neovascularization [22]. This demonstrates the multifunctional effect of the amazing CD160 receptor. More studies are needed to fully understand the specificities and the functions of this receptor and its isoforms. More recently other isoforms were unveiled including a transmembrane (TM) form and decoy receptors lacking the Iglike domain, essential for ligand binding. Unfortunately these isoforms were detected as alternative transcripts mRNA or by Western blot, but until now no antibody is able to recognize the native transmembrane form at the cell surface. CD160 can also be found as a soluble form in the serum and extracellular fluids. This soluble form is produced from the CD160-GPI by a juxta-membrane enzymatic cleavage by a phospholipase-D [4]. This soluble CD160 impaired NK activation, possibly by competing for binding to MHC-I molecules. CD160 was not only found to be expressed on NK cells but it was also detected at the surface of CD8 T cells [5,6], a minor subset of circulating CD4 T cells [7], cutaneous T cells [8,9], γδ T lymphocytes, intestinal intraepithelial T cells, activated endothelial cells [10], and mast cells [11]. Of note, whereas human B cells lack CD160 expression, B-cell chronic lymphocytic leukaemia (CLL) expresses CD160 both at the protein and mRNA level [12].However, despite this wide CD160 expression, it seems that the trans-membrane CD160 isoform expression is restricted to the NK compartment. CD160 was also found ...

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The CD160+ CD8high cytotoxic T cell subset correlates with response to HAART in HIV-1+ patients

Cited by 23 publications

References 45 publications

HIV-specific CD8+ T cells and HIV eradication

HIV-specific CD8+ T cells and HIV eradication

A Soluble Form of the MHC Class I-Specific CD160 Receptor Is Released from Human Activated NK Lymphocytes and Inhibits Cell-Mediated Cytotoxicity

CD160: A Multifunctional Cell Surface Receptor

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