Project description:Analysis of global gene expression of partial memory T cells compared to naive, effector and memory CD8+ T cells demonstrating that Tpm constitute a unique cell population with distinct global gene expression profile.
Project description:Analysis of global gene expression of partial memory T cells compared to naive, effector and memory CD8+ T cells demonstrating that Tpm constitute a unique cell population with distinct global gene expression profile.
Project description:Analysis of global gene expression of partial memory T cells compared to naive, effector and memory CD8+ T cells demonstrating that Tpm constitute a unique cell population with distinct global gene expression profile. Total RNA obtained from isolated/FACSorted murine T cells lysed in Trizol after isolation.
Project description:Analysis of global gene expression of partial memory T cells compared to naive, effector and memory CD8+ T cells demonstrating that Tpm constitute a unique cell population with distinct global gene expression profile. Total RNA obtained from isolated/FACSorted murine T cells lysed in Trizol after isolation.
Project description:Gene expression profiles of CD8+ partial memory T cells (Tpm) compared to naive, effector and memory CD8+ T cells (analysis 1, 17 samples)
Project description:Gene expression profiles of CD8+ partial memory T cells (Tpm) compared to naive, effector and memory CD8+ T cells (analysis 2, 20 samples)
Project description:<p>The efficacy of the adaptive immune response declines dramatically with age, but the cell-intrinsic mechanisms driving the changes characteristic of immune aging in humans remain poorly understood. One hallmark of immune aging is the loss of self-renewing naive cells and the accumulation of differentiated but dysfunctional cells within the CD8 T cell compartment. Using ATAC-seq, we first inferred the transcription factor binding activities that maintain the naive and central and effector memory CD8 T cell states in young adults. Integrating our results with RNA-seq, we determined that BATF, ETS1, Eomes, and Sp1 govern transcription networks associated with specific CD8 T cell subset properties, including activation and proliferative potential. Extending our analysis to aged humans, we found that the differences between memory and naive CD8 T cells were largely preserved across age, but that naive and central memory cells from older individuals exhibited a shift toward a more differentiated pattern of chromatin openness. Additionally, aged naive cells displayed a loss in chromatin openness at gene promoters, a phenomenon that appears to be due largely to a loss in binding by NRF1, leading to a marked drop-off in the ability of the naive cell to initiate transcription of mitochondrial genes. Our findings identify BATF- and NRF1-driven gene regulation as targets for delaying CD8 T cell aging and restoring T cell function.</p>
Project description:CD8 T cells normally differentiate from resting naïve T cells into function effector and then memory CD8 T cells following acute infections. During chronic viral infections, however, virus-specific CD8 T cells often become exhausted. We used microarrays to examine the gene expression differences between naive, effector, memory and exhausted virus-specific CD8 T cells following lymphocytic choriomeningitis virus infection. Experiment Overall Design: Three or four independent samples were sorted by flow cytometry for each cell type (naive, effector, memory and exhausted) virus-specific CD8 T cells. RNA was extracted and hybridized to Affymetrix microarrays.
Project description:The generation of CD8+ T-cell memory is an important aim of immunization. While several distinct subsets of CD8+ T-cell memory have been described, the lineage relationships between effector (EFF), effector memory (EM) and central memory (CM) T cells remain contentious. Specifically, there is contradictory experimental evidence to support both the linear (Naive>EFF>EM>CM) and progressive differentiation (Naive>CM>EM>EFF) models. In this study, we applied a systems biology approach to examine global transcriptional relationships between the three major CD8+ T cell subsets arising endogenously as a result of vaccination with three different prime-boost vaccine regimens. Differential gene expression analysis and principle component analysis revealed that central memory cells were more closely related to naive T cells than both effector memory and effector cells. When the transcriptional relationships between subsets were enriched in an unbiased fashion with known global transcriptional changes that result when T-cells repeatedly encounter antigen, our analysis favored a model whereby cumulative antigenic stimulation drives differentiation specifically from Naive > CM > EM > EFF. These findings provide an insight into the lineage relationship between mature CD8+ T-cell subsets and will help in the rational design of vaccines aimed at generating effective immune responses against infections and cancer. Effector (EFF), effector memory (EM), central memory (CM) and naive CD8+ T cells from mice spleen. Memory subset arise endogenously as a result of vaccination with three different prime-boost vaccine regimens: DNA-rAd5, rAd5-rAd5 and rAd5-rLCMV.
Project description:To characterize CD44low CD62low CD8 T-cell subset (P4), we compared gene expression among four CD8 T-cell subsets. A hierarchical clustering of global gene expression showed that each subset of CD8 T-cells expresses a distinct gene profile. Genes expressed in activated T-cells were highly expressed in P4 cells compared to naive P1 cells. On the other hand, genes expressed in differentiated T-cells were less expressed in P4 cells compared to either central memory (P2) or effector/memory (P3) cells. These results indicate that P4 cells are in an activated, but pre-mature state and distinct from more differentiated subsets of CD8 T-cells such as central memory and effector/memory cells.
