Mechanisms of CD8<sup>+</sup> T cell‐mediated suppression of HIV/SIV replication

McBrien, Julia Bergild; Kumar, Nitasha; Silvestri, Guido

doi:10.1002/eji.201747172

Cited by 89 publications

(94 citation statements)

References 179 publications

(219 reference statements)

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“…During acute viral infections, CD8+ T lymphocytes are able to control viral replication by producing cytokines and cytotoxic mediators 3,5 . However, when the infection becomes chronic, a persistent antigen exposure leads to the up-regulation of inhibitory receptors 3,5,12 . Also, at least in certain circumstances, it has been shown that the presence of inhibitory receptors may identify antigen specific chronically stimulated cells 16,17 .…”

Section: Polyfunctional Hiv-1 Specific Response By Cd8+ T Lymphocytesmentioning

confidence: 99%

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

Vitallé

Terrén

Gamboa-Urquijo

et al. 2020

Sci Rep

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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 ...

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Section: Polyfunctional Hiv-1 Specific Response By Cd8+ T Lymphocytesmentioning

confidence: 99%

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

Vitallé

Terrén

Gamboa-Urquijo

et al. 2020

Sci Rep

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“…Although it is still not clear what controls HIV viral load levels during the prolonged asymptomatic stage, when viral loads are relatively stable over months to years, several immune effector mechanisms are implicated, including innate responses (especially early on), antibody responses, and cellular immune responses . Among these, the most studied, and (perhaps consequently) the one for which there is the most evidence for an effect in controlling HIV, is the cellular immune response mediated by CD8+ T cells …”

Section: Hiv Immune Controlmentioning

confidence: 99%

“…In support of the first explanation, there are many experimental observations that are consistent with a noncytolytic effect of CD8+ T cells. In this context, multiple soluble factors have been found or proposed to reduce viral replication (reviewed in ). Indeed, the possibility of a nonlytic effect was also the conclusion of one of the first studies of chronically SIV‐infected macaques depleted of CD8+ cells described above, where it was found that an effect in viral production was more consistent with the data.…”

Section: Mathematical Modeling Of Cd8+ Cell Depletion Experimentsmentioning

confidence: 99%

The dynamics of simian immunodeficiency virus after depletion of CD8+ cells

Cardozo

Apetrei

Pandrea

et al. 2018

Immunological Reviews

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Human immunodeficiency virus infection is still one of the most important causes of morbidity and mortality in the world, with a disproportionate human and economic burden especially in poorer countries. Despite many years of intense research, an aspect that still is not well understood is what (immune) mechanisms control the viral load during the prolonged asymptomatic stage of infection. Because CD8+ T cells have been implicated in this control by multiple lines of evidence, there has been a focus on understanding the potential mechanisms of action of this immune effector population. One type of experiment used to this end has been depleting these cells with monoclonal antibodies in the simian immunodeficiency virus-macaque model and then studying the effect of that depletion on the viral dynamics. Here we review what these experiments have told us. We emphasize modeling studies to interpret the changes in viral load observed in these experiments, including discussion of alternative models, assumptions and interpretations, as well as potential future experiments.

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“…Additionally, HIV-1-specific CD8 T cells are also important for the control of HIV-1 replication (56). The relevance of the HIV-1-specific CD8 T cell responses has been reinforced by preclinical studies (57)(58)(59)(60).…”

Section: Discussionmentioning

confidence: 99%

Heterologous Combination of VSV-GP and NYVAC Vectors Expressing HIV-1 Trimeric gp145 Env as Vaccination Strategy to Induce Balanced B and T Cell Immune Responses

et al. 2019

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Perdiguero et al. VSV-GP/NYVAC Combination Against HIV-1 subclasses, while the other groups showed a Th2-associated IgG1 bias. In summary, our T and B cell population data demonstrated that VSV-GP-based vectors could be taken into consideration as an optimized immunogenic HIV-1 vaccine candidate component against HIV-1 when used for priming in heterologous combinations with the poxvirus vector NYVAC as a boost.

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Mechanisms of CD8⁺ T cell‐mediated suppression of HIV/SIV replication

Cited by 89 publications

References 179 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

The dynamics of simian immunodeficiency virus after depletion of CD8+ cells

Heterologous Combination of VSV-GP and NYVAC Vectors Expressing HIV-1 Trimeric gp145 Env as Vaccination Strategy to Induce Balanced B and T Cell Immune Responses

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Mechanisms of CD8+ T cell‐mediated suppression of HIV/SIV replication

Cited by 89 publications

References 179 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

The dynamics of simian immunodeficiency virus after depletion of CD8+ cells

Heterologous Combination of VSV-GP and NYVAC Vectors Expressing HIV-1 Trimeric gp145 Env as Vaccination Strategy to Induce Balanced B and T Cell Immune Responses

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Mechanisms of CD8⁺ T cell‐mediated suppression of HIV/SIV replication