CD4 T follicular helper (Tfh) cells provide the required signals to B cells for germinal center reactions that are necessary for longlived antibody responses. However, it remains unclear whether there are CD4+ memory T cells committed to the Tfh lineage after antigen clearance.
Distinct memory CD4+ T cells with commitment to T follicular helper- and T helper 1-cell lineages are generated after acute viral infection.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.
Time
View SamplesThe immune responses generated by YF-17D by profiling 20,077 genes in 25 vaccine recipients were accessed at days 1, 3, 7, and 21 post-vaccination compared to pre-vaccination in PBMCs. The immune responses generated by YF-17D by profiling 20,077 genes in 25 vaccine recipients were accessed at days 1, 3, 7, and 21 post-vaccination compared to pre-vaccination in PBMCs.
Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.
Time
View SamplesCD8 T cells play an importart role in adaptive immunity to intracellular pathogens. Nave CD8 T cells , that have not encountered antigen previously can be identified by virtue of their distinct phenotype. Upon antigenic encounter, they proliferate rapidly and undergo massive reprograming to differentiate to cytotoxic T lymphocytes. The yellow fever live virus vaccine (YF-17D) provides a model primary acute viral infection that can be used to follow this response.Here we characterize the resting, non-activated naive CD8 T cells in nine healthy adults and YF-specific CD8 T cells elicited in response to YF-17D vaccination from the same donors during the effector (2 weeks after vaccination) and memory (5-8 months later) stages.
Origin and differentiation of human memory CD8 T cells after vaccination.
Specimen part, Subject
View SamplesThese 14 samples originate from peripheral blood mononuclear cells (PBMC) from donors at different times after they were vaccinated with the YF-17D vaccine. Overall design: 10,000 to 100,000 tetramer+ CD8 T cells specific for the NS4B-214 epitope in YFV-17D were purified by flow cytometry based sorting, from 8 vaccinees. Total Naive (CD45RA+ CD8+) CD8 t cells were also sorted from these donors. Subsets were defined based on the time after vaccination. The subsets (cell types) include: Naive CD8 T cells (n=6); YFV-specific Effector CD8 T cells (day 14 after vaccination, n =3) and YFV-specific long term memory CD8 T cells (4 to 12 years after vaccination, n=5).
Origin and differentiation of human memory CD8 T cells after vaccination.
Specimen part, Subject
View SamplesCD8 T cells play roles in eliminating virus infected targets through cytotoxic effector function and are of great interest from vaccination prespective. Previous studies suggest that the cytokines produced by the CD8 T cells may contribute to the pathological consequences. Because the dengue specific memory T cells strongly secrete cytokines upon in vitro stimulation with heterologous viral antigen, the cytokine storm induced by activated T cells may contribute to the immunopathology of dengue infection. Moreover, the CD8 T cell expansion peaks before or around the time of the peak of clinical symptoms, and the frequency of activated CD8 T cells and cytokine producing cells was somewhat higher in patients with severe forms of dengue disease.
Characterization of Human CD8 T Cell Responses in Dengue Virus-Infected Patients from India.
Age, Specimen part, Disease, Disease stage
View SamplesCorrelates of immune mediated protection to most viral and cancer vaccines are still unknown. This impedes the development of novel vaccines to incurable diseases such as HIV and cancer. In this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (YF) vaccine 17D (YF17D) in a cohort of forty volunteers followed for up to one year after vaccination. We show that immunization with YF17D leads to an integrated immune response that includes several effector arms of innate immunity including complement, the inflammasome and interferons, as well as adaptive immunity as shown by an early T cell response followed by a brisk and variable B cell response. Development of these responses is preceded, as demonstrated in three independent vaccination trials and in a novel in vitro system of primary immune responses (Modular IMmune In vitro Construct (MIMIC) system), by the coordinated up-regulation of transcripts for specific transcription factors including STAT1, IRF7 and ETS2 that are upstream of the different effector arms of the immune response. These results clearly show that the immune response to a strong vaccine is preceded by coordinated induction of masters transcription factors, that lead to the development of a broad, polyfunctional and persistent immune response that integrates all effector cells of the immune system.
Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses.
No sample metadata fields
View SamplesNijmegen breakage syndrome (NBS) results from the absence of the NBS1 protein, responsible for detection of DNA double-strand breaks (DSBs). NBS is characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. Here we show successful reprogramming of NBS fibroblasts into induced pluripotent stem cells (NBS-iPSCs). Our data suggest a strong selection for karyotypically normal fibroblasts to go through the reprogramming process. NBS-iPSCs then acquire numerous chromosomal aberrations and show a delayed response to DSB induction. Furthermore, NBS-iPSCs display slower growth, mitotic inhibition, a reduced apoptotic response to stress and abnormal cell cycle-related gene expression. Importantly, NBS neural progenitor cells (NBS-NPCs) show down-regulation of neural developmental genes, which seems to be mediated by P53. Our results demonstrate the importance of NBS1 in early human development, shed new light on the molecular mechanisms underlying this severe syndrome and further expand our knowledge of the genomic stress cells experience during the reprogramming process.
Chromosomal Instability and Molecular Defects in Induced Pluripotent Stem Cells from Nijmegen Breakage Syndrome Patients.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Differential induction of TLR3-dependent innate immune signaling by closely related parasite species.
Specimen part, Cell line
View SamplesThe closely related protozoan parasites Toxoplasma gondii and Neospora caninum display similar life cycles, subcellular ultrastructure, invasion mechanisms, metabolic pathways, and genome organization, but differ in their host range and disease pathogenesis. Type II () interferon has long been known to be the major mediator of innate and adaptive immunity to Toxoplasma infection, but genome-wide expression profiling of infected host cells indicates that Neospora is a potent activator of the type I (/) interferon pathways typically associated with antiviral responses. Infection of macrophages from mice with targeted deletions in various innate sensing genes demonstrates that host responses to Neospora are dependent on the toll-like receptor Tlr3 and the adapter protein Trif. Consistent with this observation, RNA from Neospora elicits TLR3-dependent type I interferon responses when targeted to the host endo-lysosomal system. Although live Toxoplasma fail to induce type I interferon, heat-killed parasites do trigger this response, albeit much weaker than Neospora, and co-infection studies reveal that T. gondii actively suppresses the production of type I interferon. These findings reveal that eukaryotic pathogens can be potent inducers of type I interferon and that related parasite species interact with this pathway in distinct ways.
Differential induction of TLR3-dependent innate immune signaling by closely related parasite species.
Specimen part, Cell line
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