T cell dysfunction is an important feature of many chronic viral infections. In particular, it was shown that PD-1 regulates T cell dysfunction during chronic LCMV infection in mice and PD-1 high cells exhibit an intense exhausted gene signature. These findings were extended to human chronic infections such as HIV, HCV and HBV. However, it is not known if PD-1 high cells of healthy humans have the traits of exhausted cells. In this study, we provide a comprehensive description of phenotype, function and gene expression profiles of PD-1 high versus PD-1 low CD8 T cells in the peripheral blood of healthy human adults as following: 1) The percentage of naive and memory CD8 T cells varied widely in the peripheral blood cells of healthy humans and PD-1 was expressed by the memory CD8 T cells. 2) PD-1 high CD8 T cells in healthy humans did not significantly correlated with the PD-1 high exhausted gene signature of HIV specific human CD8 T cells or chronic LCMV specific CD8 T cells from mice. 3) PD-1 expression did not directly affect the ability of CD8 T cells to secrete cytokines in healthy adults. 4) PD-1 was expressed by the effector memory (TEM) compared to terminally differentiated effector (TEMRA) CD8 T cells. 5) Finally, an interesting inverse relationship between CD45RA and PD-1 expression was observed.
Phenotype, function, and gene expression profiles of programmed death-1(hi) CD8 T cells in healthy human adults.
No sample metadata fields
View SamplesBackground: Genes upregulated by low oxygen have been suggested as endogenous markers for tumor hypoxia. Yet, most of the genes investigated have shown inconsistent results, which have led to concerns about their ability to be true hypoxia markers. Previous studies have demonstrated that expression of hypoxia induced genes can be affected by extracellular pH (pH e ). Methods: Five different human cell lines (SiHa, FaDu DD, UTSCC5, UTSCC14 and UTSCC15) were exposed to different oxygen concentrations and pH (7.5 or 6.3), and gene expression analyzed with microarray (Affymetrix - Human Genome U133 Plus 2.0 Array). Results: An analysis of two of the cell lines using SAM identified 461 probesets that were able to separate the four groups Normal oxygen, normal pH , Low oxygen, normal pH , Normal oxygen, low pH and Low oxygen, low pH . From here it was possible to identify a fraction of probesets induced at low oxygen independent of pH in these two cell lines, this fraction included HIG2, NDRG1, PAI1 and RORA. Further verifi cation by qPCR highlighted the necessity of using more cell lines to obtain a robust gene expression profi les. To specifi cally select pH independent hypoxia regulated genes across more cell lines, data for FaDu DD, UTSCC5, UTSCC14 and UTSCC15 were analyzed to identify genes that were induced by hypoxia in each cell line, where the induction was not affected by low pH, and where the gene was not signifi cantly induced by low pH alone. Each cell line had 65 122 probesets meeting these criteria. For genes to be considered as target genes (hypoxia inducible pH independent), genes had to be present in three of four cell lines. Conclusion: The result is a robust hypoxia profile unaffected by pH across cell lines consisting of 27 genes. This study demonstrates a way to identify hypoxia markers by microarray, where other factors in the tumor microenvironment are taken into account.
Identifying pH independent hypoxia induced genes in human squamous cell carcinomas in vitro.
Cell line
View SamplesThis study provides a framework describing how magnetic exposure is transduced from the most-plausible molecular-level biosensor (lipid membranes) to cell-level responses that include differentiation toward neural lineages. In addition, SMF provided a stimulus that uncovered new relationships that exist even in the absence of magnetic fields between gangliosides, the time dependent regulation of IL-6 signaling by these glycolipids, and the fate of embryonic cells.
Moderate strength (0.23-0.28 T) static magnetic fields (SMF) modulate signaling and differentiation in human embryonic cells.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures.
Specimen part, Subject, Time
View SamplesWe applied a systems biology approach to study immune responses in subjects receiving 3 consecutive immunizations with RTS,S/AS01 (RRR), or in those receiving 2 immunizations of RTS,S/AS01, following a primary immunization with adenoviral Ad35 (ARR) vector expressing circumsporozoite protein.
Systems analysis of protective immune responses to RTS,S malaria vaccination in humans.
Specimen part, Disease stage, Subject, Time
View SamplesThe goal of this study is to characterize the human immune responses to the live attenuated Herpes zoster vaccine Zostavax, to understand the molecular and cellular mechanisms that lead to antibody production and T cell induction, and to understand the difference between young and elderly healthy adults. The overall data collection included antigen specific assays, flow cytometric profiling of innate and adaptive cell populations, measurement of serum cytokines, and transcriptomic and metabolomics signatures. Zostavax induced robust antigen-specific antibody responses, and significant T cell responses. A number of gene pathways were upregulated after vaccination. Using our previously developed blood transcription modules, we also identified transcriptomic correlates to antibody response. Furthermore, this study revealed strong association between PBMC transcriptomics and plasma metabolomics. Integrative analysis of orthogonal datasets from metabolomics, transcriptomic and immune profiling facilitated a temporal reconstruction of Zostavax induced biological networks culminating in antibody responses , and the delineation of novel molecular correlates of vaccine immunity.
Metabolic Phenotypes of Response to Vaccination in Humans.
Sex, Age, Specimen part, Race, Subject
View SamplesSystems approaches have been used to describe molecular signatures driving immunity to influenza vaccination in humans.
Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures.
Specimen part, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systems biology of vaccination for seasonal influenza in humans.
Specimen part, Subject, Time
View SamplesHere we applied systems approaches to investigate the innate and adaptive responses to trivalent inactivated influenza vaccine (TIV) and MF59-adjuvanted TIV (ATIV) in ninety 14-24 month old healthy children.
No associated publication
Sex, Age, Specimen part, Subject
View SamplesSystems approaches have been used to describe molecular signatures driving immunity to influenza vaccination in humans.
Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures.
Specimen part, Subject, Time
View Samples