CD300a inhibits CD16-mediated NK cell effector functions in HIV-1-infected patients

Vitallé, Joana; Terrén, Íñigo; Orrantia, Ane; Pérez-Garay, Raquel; Vidal, Francesc; Iribarren, José Antonio; Rodrı́guez, Carmen; Lirola, A M López; Bernal, Enrique; Zenarruzabeitia, Olatz; Borrego, Francisco

doi:10.1038/s41423-019-0275-4

Cited by 20 publications

(15 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, a negative correlation between CD300a expression on CD4+ T lymphocytes and markers associated with HIV-1 disease progression was discovered 38 . Lastly, we have recently reported that CD300a is up-regulated on CD56 neg NK cells from untreated HIV-1+ subjects and importantly, we demonstrated the capacity of CD300a to inhibit antibody-dependent NK cell degranulation and cytokine production in HIV-1+ individuals 31 .…”

mentioning

confidence: 55%

“…In fact, no significant differences were seen between cells from HIV negative people and HIV-1+ subjects in most of CD8+ T cell subsets. On the other hand, it has been previously described an altered expression of CD300a in other lymphocytes, including B cells, CD4+ T cells and NK cells, from HIV-1+ individuals when compared with HIV negative people 24,31,38 . Interestingly, other authors have described that CD300a expression on CD8+ T cells is not altered with cytomegalovirus (CMV) infection.…”

Section: Discussionmentioning

confidence: 97%

“…For instance, co-ligation of TCR and CD300a resulted in a decrease in intracellular Ca 2+ mobilization in CD4+ T cells, indicating that CD300a inhibits TCR-mediated signals 23 . Importantly, the crosslinking of CD300a with specific monoclonal antibodies (mAbs) is also known to diminish CD16-mediated NK cell degranulation and cytokine production in HIV-1+ individuals 31 . To conclude, we have described an up-regulation of the CD300a inhibitory receptor after the stimulation with a Gag HIV-1 peptide in cART naïve HIV-1+ patients, but undoubtedly more experiments are needed to determine the specific function of CD300a inhibitory receptor on CD8+ T cells effector functions during HIV-1 infection.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding CD8+ T cells, CD300a is differentially expressed on different subpopulations 18,19 and mRNA microarray and flow cytometry analysis of CD8+ T cells from HIV negative women showed an association of CD300a expression to a more cytotoxic molecular signature 20 . The ability of human CD300a molecule to inhibit immune processes has been demonstrated in several cell types, including TCR-mediated signalling on CD4+ T lymphocytes 22,23 , B cell receptor (BCR)-mediated signalling 24 , FcεRI and FcRγIIa-mediated signalling on basophils and mast cells 25,26 and on neutrophils 27 , respectively, and NK cell-mediated cytotoxicity and cytokine production [28][29][30][31] .…”

mentioning

confidence: 99%

See 3 more Smart Citations

Polyfunctional HIV-1 specific response by CD8+ T lymphocytes expressing high levels of CD300a

Vitallé

Terrén

Gamboa-Urquijo

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

CD300a receptor is found on different CD8+ T cell subsets and its expression has been associated to a more cytotoxic molecular signature. CD300a has an important role in some viral infections and its expression levels are known to be modulated by human immunodeficiency virus (HIV)−1 infection on several cell types. The main objective of this work was to investigate CD300a expression and its regulation during HIV-1 specific CD8+ T cell responses. CD300a receptor expression was analysed by multiparametric flow cytometry on CD8+ T lymphocytes from HIV negative donors, naive HIV-1+ individuals and HIV-1+ subjects under suppressive combined antiretroviral therapy (cART). HIV-1 specific CD8+ T cell response was studied by stimulating cells with HIV-1 derived peptides or with a GagHIV-1 peptide. Our results showed that HIV-1 specific CD8+ T cells expressing higher levels of CD300a were more polyfunctional showing an increased degranulation and cytokine production. Moreover, we observed an up-regulation of CD300a expression after Gag HIV-1 peptide stimulation. Finally, our results demonstrated an inverse correlation between CD300a expression on CD8+ T lymphocytes and HIV disease progression markers. In conclusion, CD300a expression is associated to a better and more polyfunctional HIV-1 specific CD8+ T cell response. CD8+ T cells are very important effectors in the control and clearance of viruses through several mechanisms, including granule exocytosis and cytokine production 1-3 . Many reports have shown that CD8+ T cells play a very important role in the control of viral replication during the acute phase of human immunodeficiency virus (HIV)−1 infection, contributing to the initial control of infection 1,3-7 . Thus, a large number of current studies are focused on the search of new therapies with the aim of inducing a potent and effective HIV specific CD8+ T cell response [8][9][10] .After antigen recognition and subsequent activation, CD8+ T cells up-regulate the expression of inhibitory receptors with the aim of preventing an excessive response that, if not properly regulated, could be harmful to the host 11,12 . During chronic stimulation, as for example persistent exposure to HIV antigens, CD8+ T cells became progressively dysfunctional and exhausted, and the expression of inhibitory receptors persists 13 . Exhaustion is a process characterized by a loss of proliferative capacity, differentiation and effector functions 12,14,15 . There are several inhibitory receptors that are expressed on exhausted T cells. For instance, programed cell death-1 (PD1) is known to be involved in the regulation of CD8+ T lymphocytes function during chronic HIV-1 infection and their expression correlates with disease progression 11,12,15 . In addition to the negative regulatory role of these inhibitory receptors, they also mark antigen specific T cells. For example, it has been described that PD1 on CD8+ T cells identifies the repertoire of clonally expanded tumor-reactive lymphocytes and situations of chronic inflammation, which is ...

show abstract

mentioning

confidence: 55%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Polyfunctional HIV-1 specific response by CD8+ T lymphocytes expressing high levels of CD300a

Vitallé

Terrén

Gamboa-Urquijo

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Certain subpopulations of NK cells also express the LILRB1 inhibitor receptor, also known as ILT2 and CD85j, whose ligands are a subgroup of HLA class I molecules [14]. In addition to these MHC class I specific receptors, there are other inhibitory receptors expressed by NK cells, such as TIGIT, LAIR-1, CD300a, and so forth [14,27,68].…”

Section: Cell Surface Receptors and Cytotoxic Mechanismsmentioning

confidence: 99%

NK Cell-Based Immunotherapy in Renal Cell Carcinoma

Terrén

Orrantia

Mikelez-Alonso

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Cite

Natural killer (NK) cells are cytotoxic lymphocytes that are able to kill tumor cells without prior sensitization. It has been shown that NK cells play a pivotal role in a variety of cancers, highlighting their relevance in tumor immunosurveillance. NK cell infiltration has been reported in renal cell carcinoma (RCC), the most frequent kidney cancer in adults, and their presence has been associated with patients’ survival. However, the role of NK cells in this disease is not yet fully understood. In this review, we summarize the biology of NK cells and the mechanisms through which they are able to recognize and kill tumor cells. Furthermore, we discuss the role that NK cells play in renal cell carcinoma, and review current strategies that are being used to boost and exploit their cytotoxic capabilities.

show abstract

Proteomics reveals a global phenotypic shift of NK cells in HCV patients treated with direct‐acting antivirals

Kraft

Engelskircher

et al. 2023

Eur J Immunol

View full text Add to dashboard Cite

Chronic hepatitis C virus (HCV) infections compromise natural killer (NK)‐cell immunity. Direct‐acting antivirals (DAA) effectively eliminate HCV, but the long‐term effects on NK cells in cured patients are debated. We conducted a proteomic study on CD56+ NK cells of chronic HCV‐infected patients before and 1 year after DAA therapy. Donor‐variation was observed in NK‐cell proteomes of HCV‐infected patients, with 46 dysregulated proteins restored after DAA therapy. However, 30% of the CD56+ NK‐cell proteome remained altered 1 year post‐therapy, indicating a phenotypic shift with low donor‐variation. NK cells from virus‐negative cured patients exhibited global regulation of RNA‐processing and pathways related to “stimuli response”, “chemokine signaling”, and “cytotoxicity regulation”. Proteomics identified downregulation of vesicle transport components (CD107a, COPI/II complexes) and altered receptor expression profiles, indicating an inhibited NK‐cell phenotype. Yet, activated NK cells from HCV patients before and after therapy effectively upregulated IFN‐γ and recruited CD107a. Conversely, reduced surface expression levels of Tim‐3 and 2B4 were observed before and after therapy. In conclusion, this study reveals long‐term effects on the CD56+ NK‐cell compartment in convalescent HCV patients 1 year after therapy, with limited abundance of vesicle transport complexes and surface receptors, associated with a responsive NK‐cell phenotype.

show abstract

CD300a inhibits CD16-mediated NK cell effector functions in HIV-1-infected patients

Cited by 20 publications

References 10 publications

Polyfunctional HIV-1 specific response by CD8+ T lymphocytes expressing high levels of CD300a

Polyfunctional HIV-1 specific response by CD8+ T lymphocytes expressing high levels of CD300a

NK Cell-Based Immunotherapy in Renal Cell Carcinoma

Proteomics reveals a global phenotypic shift of NK cells in HCV patients treated with direct‐acting antivirals

Contact Info

Product

Resources

About