Nelfinavir monotherapy increases naive T-cell numbers in HIV-negative healthy young adults

Vlahakis, Stacey, R.

doi:10.2741/2784

Cited by 7 publications

(3 citation statements)

References 29 publications

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“…Signal joint (sj) TREC content was assessed relative to CCR5 copies in genomic DNA (50 to 400 ng input) isolated from PBMCs. Quantitative real-time PCR for sjTREC with specific primers (forward and reverse ), Taqman probe, genomic DNA template and optimized PCR conditions in a spectrofluorometric thermal cycler (ABI PRISM 7900, PE Applied Biosystems, Foster City, CA) were used, as previously described in detail [ 25 ]. Standard curves with 1–100,000 copies of human sjTREC plasmid and human CCR5 plasmid were generated (for each plate) in order to calculate copies of TREC versus CCR5 copies (ratio) in genomic DNA for each sample.…”

Section: Methodsmentioning

confidence: 99%

The Impact of Immunosenescence on Humoral Immune Response Variation after Influenza A/H1N1 Vaccination in Older Subjects

et al. 2015

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BackgroundAlthough influenza causes significant morbidity and mortality in the elderly, the factors underlying the reduced vaccine immunogenicity and efficacy in this age group are not completely understood. Age and immunosenescence factors, and their impact on humoral immunity after influenza vaccination, are of growing interest for the development of better vaccines for the elderly.MethodsWe assessed associations between age and immunosenescence markers (T cell receptor rearrangement excision circles – TREC content, peripheral white blood cell telomerase – TERT expression and CD28 expression on T cells) and influenza A/H1N1 vaccine-induced measures of humoral immunity in 106 older subjects at baseline and three timepoints post-vaccination.ResultsTERT activity (TERT mRNA expression) was significantly positively correlated with the observed increase in the influenza-specific memory B cell ELISPOT response at Day 28 compared to baseline (p-value=0.025). TREC levels were positively correlated with the baseline and early (Day 3) influenza A/H1N1-specific memory B cell ELISPOT response (p-value=0.042 and p-value=0.035, respectively). The expression and/or expression change of CD28 on CD4+ and/or CD8+ T cells at baseline and Day 3 was positively correlated with the influenza A/H1N1-specific memory B cell ELISPOT response at baseline, Day 28 and Day 75 post-vaccination. In a multivariable analysis, the peak antibody response (HAI and/or VNA at Day 28) was negatively associated with age, the percentage of CD8+CD28low T cells, IgD+CD27- naïve B cells, and percentage overall CD20- B cells and plasmablasts, measured at Day 3 post-vaccination. The early change in influenza-specific memory B cell ELISPOT response was positively correlated with the observed increase in influenza A/H1N1-specific HAI antibodies at Day 28 and Day 75 relative to baseline (p-value=0.007 and p-value=0.005, respectively).ConclusionOur data suggest that influenza-specific humoral immunity is significantly influenced by age, and that specific markers of immunosenescence (e.g., the baseline/early expression of CD28 on CD4+ and/or CD8+ T cells and T cell immune abnormalities) are correlated with different humoral immune response outcomes observed after vaccination in older individuals, and thus can be potentially used to predict vaccine immunogenicity.

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Section: Methodsmentioning

confidence: 99%

The Impact of Immunosenescence on Humoral Immune Response Variation after Influenza A/H1N1 Vaccination in Older Subjects

et al. 2015

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“…TRECs were examined by quantitative real-time (RT)-PCR on the baseline samples (day 0) for all subjects. Signal joint (sj) TREC content was assessed relative to CCR5 copies in genomic DNA (50 to 400 ng input, isolated from PBMC) using quantitative RT-PCR with specific primers, as described previously [30]. Standard curves with known copies of human sjTREC plasmid and human CCR5 plasmid were generated in order to calculate copies of TREC versus CCR5 for test samples.…”

Section: Methodsmentioning

confidence: 99%

Leptin and leptin-related gene polymorphisms, obesity, and influenza A/H1N1 vaccine-induced immune responses in older individuals

Ovsyannikova¹,

White²,

Larrabee³

et al. 2014

Vaccine

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Obesity is a risk factor for complicated influenza A/H1N1 disease and poor vaccine immunogenicity. Leptin, an adipocyte-derived hormone/cytokine, has many immune regulatory functions and therefore could explain susceptibility to infections and poor vaccine outcomes. We recruited 159 healthy adults (5074 years old) who were immunized with inactivated TIV influenza vacci–ne that contained A/California/7/2009/H1N1 virus. We found a strong correlation between leptin concentration and BMI (r=0.55, p<0.0001), but no association with hemagglutination antibody inhibition (HAI), B-cell, or granzyme B responses. We found a slight correlation between leptin concentration and an immunosenescence marker (TREC: T-cell receptor excision circles) level (r=0.23, p=0.01). We found eight SNPs in the LEP/LEPR/GHRL genes that were associated with leptin levels and four SNPs in the PTPN1/LEPR/STAT3 genes associated with peripheral blood TREC levels (p<0.05). Heterozygosity of the synonymous variant rs2230604 in the PTPN1 gene was associated with a significantly lower (531 vs. 259, p = 0.005) TREC level, as compared to the homozygous major variant. We also found eight SNPs in the LEP/PPARG/CRP genes associated with variations in influenza-specific HAI and B-cell responses (p<0.05). Our results suggest that specific allelic variations in the leptin-related genes may influence adaptive immune responses to influenza vaccine.

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“…Theoretically these two classes of agents may be able to inhibit pyroptosis and apoptosis of cells induced to die by IFI16 and/or DNA-PK dependent pathways respectively. Cleavage of procaspase-8 by HIV protease is inhibited by HIV-protease inhibitors (PIs) [ 56 ], for which there is ample data demonstrating improvements in CD4 T cell number [ 57 ], including improvements in CD4 T cell numbers independent of antiviral effect [ 58 ]. However there are numerous off-target effects of PI, including intrinsic anti-apoptotic effects, which likely confound these observations.…”

Section: Reviewmentioning

confidence: 99%

Making sense of how HIV kills infected CD4 T cells: implications for HIV cure

Cummins¹,

Badley²

2014

Mol and Cell Ther

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Defining how HIV does, and does not, kill the host CD4 T cell that it infects is of paramount importance in an era when research is approaching a cure for infection. Three mutually exclusive pathways can lead to the death of HIV-infected cells during the HIV life cycle, before, coincident and after HIV integration and consequently may affect viral replication. We discuss the molecular mechanism underlying these pathways, the evidence supporting their roles in vivo, and contemplate how understanding these pathways might inform novel approaches to promote viral cure of HIV.

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Nelfinavir monotherapy increases naive T-cell numbers in HIV-negative healthy young adults

Cited by 7 publications

References 29 publications

The Impact of Immunosenescence on Humoral Immune Response Variation after Influenza A/H1N1 Vaccination in Older Subjects

The Impact of Immunosenescence on Humoral Immune Response Variation after Influenza A/H1N1 Vaccination in Older Subjects

Leptin and leptin-related gene polymorphisms, obesity, and influenza A/H1N1 vaccine-induced immune responses in older individuals

Making sense of how HIV kills infected CD4 T cells: implications for HIV cure

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