Project description:Central questions regarding the origin of memory CD8 T cells, their turnover and longevity in vivo are not well-defined in humans. Here, we have used the highly efficacious live yellow fever virus vaccine (YFV-17D) to address these issues in the context of a primary acute viral infection. We interrogated genome-wide CpG methylation of YFV tetramer-specific CD8 T cells. These findings provide a better understanding of how memory CD8 T cells are formed and maintained in humans.
Project description:Human Naïve-like CD8 T cells induced by the Yellow Fever Vaccine 17D were compared to the conventional subsets in total CD8 T cells Samples originate from peripheral blood mononuclear cells (PBMC) from 8 different donors vaccinated with the YF-17D vaccine 1'000 cells from various CD8 T cells subsets were purified by flow cytometry, from 8 vaccinees (donors d1 to d8); the subsets (cell types) include: A2/NS4b tetramer positive CCR7+ CD45RA+ CD8 T cells (A2_NS4b Naïve-like), Total Naive (CCR7+ CD45RA+), Total Tscm (CCR7+ CD45RA+ CD58+ CD95+), Total CM (CCR7+ CD45RA-) and Total Effectors (CCR7 negative).
Project description:Human Naïve-like CD8 T cells induced by the Yellow Fever Vaccine 17D were compared to the conventional subsets in total CD8 T cells Samples originate from peripheral blood mononuclear cells (PBMC) from 8 different donors vaccinated with the YF-17D vaccine
Project description:Immune response to infection involves the regulation of numerouse genes in numerous cell types. The number and type of genes that become differentially expressed in response to infection can result in very different pathophysiologic presentations and disease course. Wild type YFV and 17D despite having very few genetic differences result in very different disease outcomes in human and monkey hosts. We used microarrays to detail the global programme of gene expression of Rhesus macaque immune cells responding to both wild type and 17D strains of YFV. We identified distinct classes of gene expression as well as marked differences in differential gene expression between responses to 17D and wild type strains of YFV. Rhesus PBMC were isolated before and on day 3 of either vaccination with 17D or infection with wild type YFV with an n of 3 per group. Total RNA was extracted and hybridized on Affymetrix microarrays.
Project description:We tested the effects of co-infection on vaccine response to YFV-17D. Groups of mice were divided into either Mock infected or Co-infected groups. Mock infected were housed in a biohazard facility and inoculated with PBS. Co-infected were infected sequentially with murine gammaherpesvirus-68, murine cytomegalovirus, influenza WSN, and Heligmosimoides polygyrus. Both mock and co-infected groups were challenged with Yellow Fever virus (YFV-17D). Day 0 is prior to YFV. Days 3, 7, and 21 were timepoints after YFV.
Project description:Immune response to infection involves the regulation of numerouse genes in numerous cell types. The number and type of genes that become differentially expressed in response to infection can result in very different pathophysiologic presentations and disease course. Wild type YFV and 17D despite having very few genetic differences result in very different disease outcomes in human and monkey hosts. We used microarrays to detail the global programme of gene expression of Rhesus macaque immune cells responding to both wild type and 17D strains of YFV. We identified distinct classes of gene expression as well as marked differences in differential gene expression between responses to 17D and wild type strains of YFV.
Project description:CD8 T cells play an importart role in adaptive immunity to intracellular pathogens. Naïve 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.
