Healthy Neonates Possess a CD56-Negative NK Cell Population with Reduced Anti-Viral Activity

Jacobson, Amanda; Bell, F; Lejarcegui, Nicholas; Mitchell, Caroline; Frenkel, Lisa M.; Horton, Helen

doi:10.1371/journal.pone.0067700

Cited by 24 publications

(28 citation statements)

References 47 publications

(79 reference statements)

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“…We also observed a modest correlation between the suppressive capacity of bulk NK cells and the percentage of acutely activated CD69 + CD16 − CD56 + NK cells from all infants in our cohort. This finding again suggests that activation of these cytokine-producing NK cells may be an important component for suppressing viral replication in this assay, in agreement with previous studies [12,38]. Further studies are warranted to examine the direct role of NK cell derived cytokines in HIV-1 transmission.…”

Section: Discussionsupporting

confidence: 91%

“…Interestingly, cases trended towards underrepresentation of CD16 + CD56 − NK cells (4.1 and 14.1%; P = 0.07) compared with controls, and these findings were also found in the refined gating strategy analysis (supplemental digital content 2, http://links.lww.com/QAD/A505). This population has been previously described as immature [12,13,31,32], suggesting a potential protective effect of having a larger pool of NK cells able to undergo differentiation into mature NK cells associated with effector functions.…”

Section: Resultsmentioning

confidence: 95%

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Natural killer cell and T-cell subset distributions and activation influence susceptibility to perinatal HIV-1 infection

Gasper

Kunwar

Itaya

et al. 2014

Aids

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Objective To determine neonatal immunologic factors that correlate with mother-to-child-transmission of HIV-1. Design This case–control study compared cord blood natural killer (NK) and T-cell populations of HIV-1 exposed infants who subsequently acquired infection by 1 month (cases) to those who remained uninfected by 1 year of life (controls). Control specimens were selected by proportional match on maternal viral load. Methods Cryopreserved cord blood mononuclear cells (CBMCs) were thawed and stained for multiparameter flow cytometry to detect NK and T-cell subsets and activation status. CBMCs were also used in a viral suppression assay to evaluate NK cell inhibition of HIV-1 replication in autologous CD4+ T cells. Results Cord blood from cases contained a skewed NK cell repertoire characterized by an increased proportion of CD16−CD56+ NK cells. In addition, cases displayed less-activated CD16−CD56+ NK cells and CD8+ T cells, based on HLA-DR+CD38+ costaining. NK cell suppression of HIV-1 replication ex vivo correlated with the proportion of acutely activated CD68+CD16−CD56+ NK cells. Finally, we detected a higher proportion of CD27−CD45RA− effector memory CD4+ and CD8+ T cells in cord blood from cases compared with controls. Conclusion When controlled for maternal viral load, cord blood from infants who acquired HIV-1 had a higher proportion of CD16−CD56+ NK cells, lower NK cell activation and higher levels of mature T cells (potential HIV-1 targets) than control infants who remained uninfected. Our data provide evidence that infant HIV-1 acquisition may be influenced by both innate and adaptive immune cell phenotypes and activation status.

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Section: Discussionsupporting

confidence: 91%

Section: Resultsmentioning

confidence: 95%

Natural killer cell and T-cell subset distributions and activation influence susceptibility to perinatal HIV-1 infection

Gasper

Kunwar

Itaya

et al. 2014

Aids

Self Cite

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“…With respect to their donor‐independent and subset‐specific inventory, CD56 neg NK cells were found to be well equipped for performing cellular cytotoxicity. While expression of GrzB was previously reported for the CD56 neg population , we here characterised expression patterns of all five granzymes. Interestingly, GrzH and M were detected with the highest abundance in CD56 neg as compared to CD56 dim and CD56 bright NK cells.…”

Section: Discussionmentioning

confidence: 81%

Proteome analysis of human CD56^neg NK cells reveals a homogeneous phenotype surprisingly similar to CD56^dim NK cells

et al. 2018

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NK cells lacking CD56 (CD56 ) were first identified in chronic HIV-1 infection. However, CD56 NK cells also exist in healthy individuals, albeit in significantly lower numbers. Here, we provide an extensive proteomic characterisation of human CD56 peripheral blood NK cells of healthy donors and compare them to their CD56 and CD56 counterparts. Unbiased large-scale surface receptor profiling clustered CD56 cells as part of the main NK cell compartment and indicated an overall CD56 -like phenotype. Total proteome analyses of CD56 NK cells further confirmed their similarity with CD56 NK cells, and revealed a complete cytolytic inventory with high levels of perforin and granzyme H and M. In the present study, twelve proteins discriminated CD56 NK cells from CD56 NK cells with nine up-regulated and three down-regulated proteins in the CD56 NK cell population. Those proteins were functionally related to lytic granule composition and transport, interaction with the extracellular matrix, DNA transcription or repair, and proliferation. Corroborating these results, CD56 NK cells showed modest cytotoxicity, degranulation, and IFN-ɣ secretion as compared to CD56 NK cells. In conclusion, CD56 NK cells constitute functionally competent cells sharing many features of bona fide CD56 NK cells in healthy individuals, but with some distinct characteristics.

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“…Studies of human infants showed that neonates had significantly lower NK cell lytic activity and the activity was further reduced by infection or sepsis (Georgeson et al, 2001;Uksila et al, 1982). NK cells of infants also had reduced antiviral activity such as defective killing of virus infected cells and reduced cytokine secretion (Jacobson et al, 2013). Collectively, reduced NK cell activity and NK cell frequencies may have contributed to the early onset of virus shedding and the severe clinical signs in the suckling versus weaned pigs.…”

Section: Discussionmentioning

confidence: 99%

Age-dependent variation in innate immune responses to porcine epidemic diarrhea virus infection in suckling versus weaned pigs

Annamalai

Saif

et al. 2015

Veterinary Immunology and Immunopathology

104

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Porcine epidemic diarrhea (PED) is an enteric coronaviral infection that causes severe morbidity and mortality in suckling pigs, but less severe disease in older pigs. Consequently, it causes significant economic losses to the pork industry. There are limited studies on the innate immune responses to PED virus (PEDV) in pigs. The aims of our study were to investigate differences in innate immune responses to PEDV infection in suckling and weaned pigs and to examine if disease severity coincides with reduced innate immune responses. Weaned 26-day-old pigs (n=20) and 9-day-old nursing pigs (n=20) were assigned to PEDV inoculated or uninoculated control groups. The pigs were observed daily for clinical signs, virus shedding and were euthanized at post-inoculation days (PIDs) 1 and 5 to assay immune responses. Blood samples were collected at PIDs 1, 3 and 5. The natural killer (NK) cell frequencies, NK cell activities (lysis of target K562 tumor cells in vitro), CD3+CD4+ T cell and CD3+CD8+ T cell frequencies were measured in blood and ileum at PIDs 1 and 5. The PEDV infected suckling pigs showed severe diarrhea and vomiting at PID 1, whereas the PEDV infected weaned pigs showed milder clinical signs starting at PID 3. PEDV infected suckling pigs had significantly higher diarrhea scores, earlier fecal PEDV RNA shedding and significantly higher viremia (viral RNA in serum) compared to weaned pigs. There was no mortality in either infected suckling or infected weaned pigs. The control pigs not inoculated with PEDV did not show any clinical signs and no detectable fecal or serum PEDV RNA. Strikingly, PEDV infected suckling pigs had significantly lower NK cell frequencies, undetectable NK cell activity and lower IFNγ producing NK cells in blood and ileum compared to PEDV infected weaned pigs. Pro-inflammatory cytokine profiles of PEDV infected suckling pigs differed from those of PEDV infected weaned pigs and coincided with onset of fecal PEDV RNA shedding and serum PEDV RNA titers. The infected suckling pigs have higher and earlier increases in serum IFNα, but lower serum IL-8 and TNFα levels compared to infected weaned pigs. CD3+CD4+ T cell frequencies were significantly higher in ileum of suckling pigs than in weaned pigs, whereas there was no difference in CD3+CD8+ T cell frequencies. In conclusion, the observations of impaired lytic activity and IFN-γ production by NK cells in suckling pigs coincided with the increased severity of PEDV infection in the suckling pigs compared with the weaned pigs.

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Healthy Neonates Possess a CD56-Negative NK Cell Population with Reduced Anti-Viral Activity

Cited by 24 publications

References 47 publications

Natural killer cell and T-cell subset distributions and activation influence susceptibility to perinatal HIV-1 infection

Natural killer cell and T-cell subset distributions and activation influence susceptibility to perinatal HIV-1 infection

Proteome analysis of human CD56^neg NK cells reveals a homogeneous phenotype surprisingly similar to CD56^dim NK cells

Age-dependent variation in innate immune responses to porcine epidemic diarrhea virus infection in suckling versus weaned pigs

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Healthy Neonates Possess a CD56-Negative NK Cell Population with Reduced Anti-Viral Activity

Cited by 24 publications

References 47 publications

Natural killer cell and T-cell subset distributions and activation influence susceptibility to perinatal HIV-1 infection

Natural killer cell and T-cell subset distributions and activation influence susceptibility to perinatal HIV-1 infection

Proteome analysis of human CD56neg NK cells reveals a homogeneous phenotype surprisingly similar to CD56dim NK cells

Age-dependent variation in innate immune responses to porcine epidemic diarrhea virus infection in suckling versus weaned pigs

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Proteome analysis of human CD56^neg NK cells reveals a homogeneous phenotype surprisingly similar to CD56^dim NK cells