Low Proportions of CD28− CD8+ T cells Expressing CD57 Can Be Reversed by Early ART Initiation and Predict Mortality in Treated HIV Infection

Lee, Sulggi; Sinclair, Elizabeth; Jain, Vivek; Huang, Yong; Epling, Lorrie; Natta, Mark Van; Meinert, Curtis L.; Martin, Jeffrey N.; McCune, Joseph M.; Deeks, Steven G.; Lederman, Michael M.; Hecht, Frederick M.; Hunt, Peter W.

doi:10.1093/infdis/jiu109

Cited by 51 publications

(46 citation statements)

References 25 publications

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“…Additionally, low proportions of CD28 Ϫ CD8 ϩ T cells expressing CD57 were a predictive marker of mortality among ART-treated HIV-infected patients with advanced disease (16). These recent data point toward a positive role for CD57-expressing CD8 ϩ T cell subsets, presumably due to their high cytolytic activity, in contrast to the deleterious impact of immune senescence, usually associated with the CD57-expressing subsets.…”

Section: Uring Chronic Hiv Infection Virus-specific Cd8mentioning

confidence: 87%

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High Eomesodermin Expression among CD57 ⁺ CD8 ⁺ T Cells Identifies a CD8 ⁺ T Cell Subset Associated with Viral Control during Chronic Human Immunodeficiency Virus Infection

Simonetta

Hua

Lécuroux

et al. 2014

J Virol

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During HIV infection, increased CD57 expression among CD8؉ T cells has been associated with immune senescence and defective immune responses. Interestingly, CD57-expressing CD8؉ T cells exhibit a dual profile, being simultaneously highly cytotoxic (terminally differentiated effectors) and poorly proliferative (replicative senescent). Recent publications point toward a positive role of CD57-expressing CD8 ؉ T cell subsets, presumably due to their high cytolytic activity. We further investigated the phenotype of CD57-expressing CD8 ؉ T cells in healthy donors and during HIV infection combining CD57 expression to Eomesodermin (EOMES), a T box transcription factor which determines, coordinately with T-bet, effector and memory CD8 ؉ T cell differentiation. We defined in healthy donors two functionally distinct CD57-expressing CD8 primary infected patients, long-term viremic patients, aviremic patients treated with antiretroviral therapy, and HIV controllers; we demonstrated a higher percentage of CD57-expressing cells in all HIV-infected patients regardless of virological status. When heterogeneity in EOMES expression among CD57 cells was taken into account, we detected significantly higher proportions of EOMES hi CD57؉ cells among HIV-specific and nonspecific CD8 ؉ T cells from HIV controllers than in aviremic antiretroviral-treated patients and viremic patients. Importantly, such a peculiar non-terminally differentiated EOMES hi CD57 ؉ phenotypic profile was associated with viral control. IMPORTANCEThis study demonstrates that functional heterogeneity exists among CD57-expressing CD8 T cells, which include both terminally differentiated, highly cytotoxic EOMES int CD57 ؉ CD8 ؉ T cells and less differentiated EOMES hi CD57 ؉ CD8 T cells, which do not exhibit immediate cytotoxic functions but present high proliferative capacity. Interestingly, HIV controllers present a high proportion of EOMES hi CD57 cells among CD57-expressing HIV-specific CD8 T cells compared to both long-term viremic and aviremic antiretroviral therapy (ART)-treated patients, suggesting a beneficial role for this cell subset in viral control.

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Section: Uring Chronic Hiv Infection Virus-specific Cd8mentioning

confidence: 87%

“…Ϫ CD8 ϩ T cells were increased following ART treatment (16). Additionally, low proportions of CD28 Ϫ CD8 ϩ T cells expressing CD57 were a predictive marker of mortality among ART-treated HIV-infected patients with advanced disease (16).…”

Section: Uring Chronic Hiv Infection Virus-specific Cd8mentioning

confidence: 98%

High Eomesodermin Expression among CD57 ⁺ CD8 ⁺ T Cells Identifies a CD8 ⁺ T Cell Subset Associated with Viral Control during Chronic Human Immunodeficiency Virus Infection

Simonetta

Hua

Lécuroux

et al. 2014

J Virol

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“…Interestingly, the set point viral load was inversely correlated with the presence of CD57 ϩ cytolytic CD4 ϩ T cells during acute infection. This observation is particularly interesting in light of a recent study that also found that the frequency of CD57 ϩ expressing CD8 ϩ T cells is inversely correlated with HIV progression, suggesting a cooperative role for these cytotoxic cell subsets to control HIV loads in chronic infection (34). To probe this possibility, we tested the ability of CD57 ϩ CD4 ϩ T cells and cytotoxic CD8…”

Section: Although Cd4mentioning

confidence: 93%

Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia

Johnson

Eller

Teigler

et al. 2015

J Virol

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“…Conversely, hypercoagulability (i.e. D-dimer elevations) and some adaptive immune defects are nearly completely reversed by very early ART [14, 15], suggesting that some pathways of HIV-associated immune dysfunction (and presumably their drivers) require at least several months of untreated infection before defects become irreversible. This is an important point as the two largest clinical trials of early ART (START and Temprano) primarily demonstrated benefit of this strategy in reducing infectious complications and malignancies (mostly infection-associated), with less evidence for a robust decline in cardiovascular events [16, 17].…”

Section: Persistent Immune Activation During Artmentioning

confidence: 99%

Role of immune activation in progression to AIDS

Utay

Hunt

2016

Current Opinion in HIV and AIDS

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Purpose of the review To review recent insights into the impact of HIV-associated immune activation on AIDS and non-AIDS morbidity and mortality. Recent findings Immune activation has long been recognized as an important consequence of untreated HIV infection and predictor of AIDS progression, which declines but fails to normalize during suppressive antiretroviral therapy (ART), and continues to predict disease in this setting. Thus, a major research agenda is to develop novel therapies to reduce persistent immune activation in treated HIV infection. Yet, the optimal targets for interventions remain unclear. Both the specific root causes of immune activation and the many interconnected pathways of immune activation that are most likely to drive disease risk in HIV-infected individuals remain incompletely characterized, but recent studies have shed new light on these topics. Summary In the context of this review, we will summarize recent evidence helping to elucidate the immunologic pathways that appear most strongly predictive of infectious and non-infectious morbidity. We will also highlight the likelihood that not all root drivers of immune activation - and the discrete immunologic pathways to which they give rise - are likely to produce the same disease manifestations and/or be equally attenuated by early ART initiation.

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Low Proportions of CD28− CD8+ T cells Expressing CD57 Can Be Reversed by Early ART Initiation and Predict Mortality in Treated HIV Infection

Abstract: Abnormally low proportions of CD28(-)CD8(+) T cells expressing CD57 predict increased mortality during treated HIV infection and may be reversed with early ART initiation.

Cited by 51 publications

References 25 publications

High Eomesodermin Expression among CD57 ⁺ CD8 ⁺ T Cells Identifies a CD8 ⁺ T Cell Subset Associated with Viral Control during Chronic Human Immunodeficiency Virus Infection

High Eomesodermin Expression among CD57 ⁺ CD8 ⁺ T Cells Identifies a CD8 ⁺ T Cell Subset Associated with Viral Control during Chronic Human Immunodeficiency Virus Infection

Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia

Role of immune activation in progression to AIDS

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Low Proportions of CD28− CD8+ T cells Expressing CD57 Can Be Reversed by Early ART Initiation and Predict Mortality in Treated HIV Infection

Abstract: Abnormally low proportions of CD28(-)CD8(+) T cells expressing CD57 predict increased mortality during treated HIV infection and may be reversed with early ART initiation.

Cited by 51 publications

References 25 publications

High Eomesodermin Expression among CD57 + CD8 + T Cells Identifies a CD8 + T Cell Subset Associated with Viral Control during Chronic Human Immunodeficiency Virus Infection

High Eomesodermin Expression among CD57 + CD8 + T Cells Identifies a CD8 + T Cell Subset Associated with Viral Control during Chronic Human Immunodeficiency Virus Infection

Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia

Role of immune activation in progression to AIDS

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Product

Resources

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High Eomesodermin Expression among CD57 ⁺ CD8 ⁺ T Cells Identifies a CD8 ⁺ T Cell Subset Associated with Viral Control during Chronic Human Immunodeficiency Virus Infection

High Eomesodermin Expression among CD57 ⁺ CD8 ⁺ T Cells Identifies a CD8 ⁺ T Cell Subset Associated with Viral Control during Chronic Human Immunodeficiency Virus Infection