CD56−CD16+ NK cells from HIV-infected individuals negatively regulate IFN-γ production by autologous CD8+ T cells

Ma, Meichen; Yin, Xu; Zhao, Xue; Guo, Chenxi; Zhu, Xiaoyu; T, Liu; Yang, Mei; Zhang, Zining; Fu, Yajing; Liu, Jing; Xu, Junjie; Ding, Haibo; Han, Xiaoxu; Chu, Zhenxing; Shang, Hong; Jiang, Yongjun

doi:10.1002/jlb.3a0819-171rr

Cited by 13 publications

(10 citation statements)

References 47 publications

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“…Then, we analyzed the subsets of NK cells. CD16 and CD56 were used to distinguish the subsets of NK cells as described previously ( 11 ) ( Figure S2A ). Compared to healthy controls, the COVID-19 patients showed significantly increased percentage of CD3 - CD56 bright CD16 neg/dim cells, and CD3 - CD56 dim CD16 - cells ( Figure S2B ).…”

Section: Resultsmentioning

confidence: 99%

Elevated Exhaustion Levels of NK and CD8+ T Cells as Indicators for Progression and Prognosis of COVID-19 Disease

et al. 2020

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Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induced Coronavirus Disease 2019 (COVID-19) has posed a global threat to public health. The immune system is crucial in defending and eliminating the virus and infected cells. However, immune dysregulation may result in the rapid progression of COVID-19. Here, we evaluated the subsets, phenotypic and functional characteristics of natural killer (NK) and T cells in patients with COVID-19 and their associations with disease severity. Methods Demographic and clinical data of COVID-19 patients enrolled in Wuhan Union Hospital from February 25 to February 27, 2020, were collected and analyzed. The phenotypic and functional characteristics of NK cells and T cells subsets in circulating blood and serum levels of cytokines were analyzed via flow cytometry. Then the LASSO logistic regression model was employed to predict risk factors for the severity of COVID-19. Results The counts and percentages of NK cells, CD4 + T cells, CD8 + T cells and NKT cells were significantly reduced in patients with severe symptoms. The cytotoxic CD3 - CD56 dim CD16 + cell population significantly decreased, while the CD3 - CD56 dim CD16 - part significantly increased in severe COVID-19 patients. More importantly, elevated expression of regulatory molecules, such as CD244 and programmed death-1 (PD-1), on NK cells and T cells, as well as decreased serum cytotoxic effector molecules including perforin and granzyme A, were detected in patients with COVID-19. The serum IL-6, IL-10, and TNF-α were significantly increased in severe patients. Moreover, the CD3 - CD56 dim CD16 - cells were screened out as an influential factor in severe cases by LASSO logistic regression. Conclusions The functional exhaustion and other subset alteration of NK and T cells may contribute to the progression and improve the prognosis of COVID-19. Surveillance of lymphocyte subsets may in the future enable early screening for signs of critical illness and understanding the pathogenesis of this disease.

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Section: Resultsmentioning

confidence: 99%

Elevated Exhaustion Levels of NK and CD8+ T Cells as Indicators for Progression and Prognosis of COVID-19 Disease

et al. 2020

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“…Importantly, the presence of CD56-NK cells in CHB patients was independent of their human cytomegalovirus (HCMV) serological status (Figure S7), a life-long persistent viral infection that has been known to remarkably impact the NK cell compartment and effector functions. 29,[58][59][60][61] Thus, in line with other persistent viral infections such as HIV, [24][25][26]62 HCV 27,28 and HCMV, 61 chronic HBV infection has a significant impact on the NK cell compartment, resulting in expansion of CD56-NK cells. Considering the accumulation of CD56-NK cells can be found in many different pathological and physiological contexts, the mechanisms related to their presence is likely related to immune system activation rather than specific to viral infection per se.…”

Section: Discussionmentioning

confidence: 99%

Expansion of dysfunctional CD56‐CD16+ NK cells in chronic hepatitis B patients

Wijaya

Read

Schibeci

et al. 2021

Liver International

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Background & Aims: Natural killer (NK) cells are primary innate effector cells that play an important role in the control of human viral infections. During chronic viral infection, NK cells undergo significant changes in phenotype, function and subset distribution, including the appearance of CD56-CD16+ (CD56-) NK cells, previously identified in chronic human immunodeficiency virus (HIV) and hepatitis C virus infection. However, the presence of CD56-NK cells in the pathogenesis of chronic hepatitis B (CHB) remains unknown. Methods: Phenotype and function of CD56-NK cells from patients with CHB (n = 28) were assessed using flow cytometry and in vitro stimulation with HBV antigen. Results: CHB patients had a higher frequency of CD56-NK cells compared to healthy controls in peripheral blood (6.2% vs 1.4%, P < .0001). Compared to CD56+ NK cells, CD56-NK cells had increased expression of inhibitory receptors, and reduced expression of activating receptors, as measured by MFI and qPCR. CD56-NK cells were less responsive to target cell and cytokine stimulation compared to their CD56+ counterparts. In addition, CD56-NK cells demonstrated defective dendritic cells (DCs) interactions resulting in reduced DCs maturation, lower expression of NK CD69 and impaired capacity of NK cells to eliminate immature DCs in co-culture studies. Finally, frequency of CD56-NK cells was positively correlated with serum HBV DNA levels. Conclusion: Chronic HBV infection induces the expansion of highly dysfunctionalof CD56-NK cells that likely contribute to inefficient innate and adaptive antiviral immune response in chronic HBV infection.

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“…9 Of note, CD56 -CD16 + NK cells can suppress IFN-c production by CD8 + T cells. 28 Indeed, high plasma viral load is associated with higher frequencies of CD56 -CD16 + cells. 29 On the contrary, the presence of these cells may reflect recent degranulation of more functional cells.…”

Section: Discussionmentioning

confidence: 99%

Timing of Antiretroviral Therapy Initiation Determines Rectal Natural Killer Cell Populations

Utay

Vigil

Somasunderam

et al. 2020

AIDS Research and Human Retroviruses

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Despite antiretroviral therapy (ART), innate and adaptive immunologic damage persists in the periphery and gut. T memory stem cells (Tscm) and natural killer (NK) cells are pivotal for host defense. Tscm are memory cells capable of antigen response and self-renewal, and circulating and gut NK cell populations may facilitate HIV control. The impact of early ART on circulating and gut Tscm and NK cells is unknown. We enrolled participants who initiated ART during acute versus chronic HIV-1 infection versus no ART in chronic infection. We performed flow cytometry to identify NK and Tscm cells in the blood and rectum and polymerase chain reaction to quantify the HIV-1 reservoir in both sites. We used the Mann-Whitney U-test and Spearman correlation coefficients for analysis. Participants who started ART in acute infection had lower rectal CD56 bright CD16 dim cell frequencies than participants who started ART in chronic HIV-1 infection and lower CD56 bright and CD56 bright CD16cell frequencies than participants with chronic infection without ART. Higher circulating NK cell, CD56-CD16 bright , CD56 dim , and CD56 dim CD16 bright frequencies correlated with higher HIV-1 DNA levels in rectal CD4 + T cells, whereas higher circulating CD4 + T cell counts correlated with higher rectal NK, CD56 bright CD16 dim , and CD56 dim CD16 bright frequencies. Peripheral CD56 bright CD16cells were inversely associated with rectal CD56-CD16 bright cells. Rectal CD8 + Tscm frequencies were higher in participants without ART than participants with chronic infection on ART. Timing of ART initiation determines rectal NK cell populations, and ART may influence rectal Tscm populations. Whether the gut reservoir contributes to NK cell activation requires further study.

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CD56−CD16+ NK cells from HIV-infected individuals negatively regulate IFN-γ production by autologous CD8+ T cells

Cited by 13 publications

References 47 publications

Elevated Exhaustion Levels of NK and CD8+ T Cells as Indicators for Progression and Prognosis of COVID-19 Disease

Elevated Exhaustion Levels of NK and CD8+ T Cells as Indicators for Progression and Prognosis of COVID-19 Disease

Expansion of dysfunctional CD56‐CD16+ NK cells in chronic hepatitis B patients

Timing of Antiretroviral Therapy Initiation Determines Rectal Natural Killer Cell Populations

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