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MiRNA signatures of antigen specific CD8+ T cells at different stages of immune response to LCMV infection

ABSTRACT: miRNAs play an important role in regulating CD8+ T cell response. We used the microarray approach to profile the miRNA signatures of naïve, day 5 effector, day 8 effector, and memory CD8+ T cells. We identified a miRNA signature associated with rapidly proliferating effector CD8+ T cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE34216 | GEO | 2012/06/05

SECONDARY ACCESSION(S): PRJNA156547

REPOSITORIES: GEO

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miRNA signatures of antigen specific CD8+ T cells at different stages of immune response to LCMV infection

Project description:miRNAs play an important role in regulating CD8+ T cell response. We used the microarray approach to profile the miRNA signatures of naïve, day 5 effector, day 8 effector, and memory CD8+ T cells. We identified a miRNA signature associated with rapidly proliferating effector CD8+ T cells. CD8+ T cells from P14 TCR transgenic mice were transferred to C57BL6 recipients which were subsequently infected with LCMV Armstrong. Donor P14 CD8+ T cells were sorted on day 5, day 8, or >day 60 post-infection. Naïve P14 CD8+ T cells were sorted directly from naive P14 splenocytes. The total RNA including miRNAs was extracted from sorted samples, labeled, and hybridized to Agilent Mouse miRNA microarray.

2012-06-04 | E-GEOD-34216 | biostudies-arrayexpress

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Project description:Understanding the response of memory CD8 T cells to persistent antigen re-stimulation and the role of CD4 T cell help is critical to the design of successful vaccines for chronic diseases. However, studies comparing the protective abilities and qualities of memory and naïve cells have been mostly performed in acute infections, and little is known about their roles during chronic infections. Herein, we show that memory cells dominate over naïve cells and are protective when present in large enough numbers to quickly reduce infection. In contrast, when infection is not rapidly reduced, memory cells are quickly lost, unlike naïve cells. This loss of memory cells is due to (i) an early block in cell proliferation, (ii) selective regulation by the inhibitory receptor 2B4, and (iii) increased reliance on CD4 T cell help. These findings have important implications towards the design of T cell vaccines against chronic infections and tumors. 16 samples are analyzed: 3 replicates of secondary effector CD8 P14 T cells at day 8 post-acute lymphocytic choriomeningitis virus (LCMV) infection; 4 replicates of secondary effector CD8 P14 T cells at day 8 post-chronic LCMV infection; 4 replicates of primary effector CD8 P14 T cells at day 8 post-acute LCMV infection; and 5 replicates of primary effector CD8 P14 T cells at day 8 post-chronic LCMV infection.

2011-08-22 | E-GEOD-30962 | biostudies-arrayexpress

Longitudinal expression data from CD8+ T cells responding to LCMV-Armstrong or LCMV-Clone 13

Project description:During acute viral infections, naïve CD8+ T cells differentiate into effector CD8+ T cells and, after viral control, into memory CD8+ T cells. Memory CD8+ T cells are highly functional, proliferate rapidly upon reinfection and persist long-term without antigen. In contrast, during chronic infections, CD8+ T cells become “exhausted” and have poor effector function, express multiple inhibitory receptors, possess low proliferative capacity, and cannot persist without antigen. To compare the development of functional memory T cells with poorly functional exhausted T cells, we generated longitudinal transcriptional profiles for each. Naive CD44Lo CD8+ T cells were isolated and sorted from uninfected C57BL/6 mice and H2-Db GP33-specific CD8+ T cells were sorted using MHC-I tetramers at d6, 8, 15, and 30 p.i. with either LCMV Arm or LCMV clone 13. RNA from these CD8+ T cells was processed, amplified, labeled, and hybridized to Affymetrix GeneChip MoGene 1.0 st microarrays

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Gene expression profile of influenza virus antigen-activated or in vitro stimulated murine CD8+ T cells on day 7

Project description:The precise timing and pathway of memory CD8+ T cells differentiation from naïve T cells have remained undetermined. We found the smaller cell-size and slower cell cycling cells were segregated from the proliferative larger cell-size activated T cell pool at the peak of infection. Gene signature of the smaller cell-size slower cycling cells and the large cell-size proliferative cells was compared to the signature of naïve, effector, central and effector memory CD8+ T cells. Total RNA samples were prepared from sorted populations of larger or smaller cell-sized cells from spleens of influenza virus PR8-OVA-infected mice on day 7 p.i. or from in vitro 7 days culture after stimulation with plate-bound anti-CD3ε (1.0 μg ml−1) and anti-CD28 mAb (0.5 μg ml−1). Effector T-cell control samples were prepared from SIINFEKL (100 ng ml−1) stimulated OT-I cells after 4 days of in vitro culture with rIL-2 (10 ng/ml) and sorted as CD8+CD44hiCD62Llo. Control bona fide effector memory and central memory T cells were sorted from the spleens of PR8-OVA-infected mice on day 42 p.i. Naive cells were sorted as CD8+CD44loCD62Lhi cells from uninfected C57BL/6 mice.

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Longitudinal expression data from CD8+ T cells responding to LCMV-Armstrong or LCMV-Clone 13

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Gene expression in LCMV-specific Blimp-1 deficient effector CD8+ T cells compared to wildtype effector CD8+ T cells

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H3K27Ac ChIP-seq of P14 CD8 T cells during acute LCMV infection

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Project description:CD4 and CD8 T cells display functional defects during chronic infection such as loss of certain cytokines. Recent studies have suggested that CD4 T cells may actually gain other functions, however. Here, we analyzed gene expression profiles from LCMV-specific CD4 and CD8 T cells throughout the response to either acute LCMV or chronic LCMV infection. This alllowed us to identify CD4-specific changes during chronic infection compared to acute infection but also revealed shared core regulators between CD4 and CD8 T cells. LCMV-specific CD4 and CD8 T cells were isolated 6, 8, 15 and 30 days post infection with LCMV Armstrong or LCMV clone 13. Naïve CD4 and CD8 T cells were also isolated from naïve mice as comparisons. Four replicates of each sample were hybridized. The only exception is LCMV-specific CD4 T cells isolated 6 days post infection with LCMV-Arm where only three replicates were hybridized.

2012-12-12 | E-GEOD-30431 | biostudies-arrayexpress

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