Splenic CD8+ T cells in chronic LCMV infection
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PROVIDER: PRJEB43201 | ENA |
REPOSITORIES: ENA
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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
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
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.
2012-12-12 | GSE30431 | GEO
Project description:T cells specific for a certain antigen are a heterogeneous population characterized by cells expressing different T Cell Receptors (TCRs). As the TCR determines the avidity of a T cell clone for its cognate antigen, this feature has also a significant impact on the fate of such clone during antigenic challenge. In the context of chronic viral infection, T cells specific for the chronic virus differentiate into exhausted cells with limited functionality. We find that, in the process of exhaustion following infection with LCMV-Clone13, certain clones of CD8 T cells specific for the LCMV immunodominant epitope GP33 are enriched compared to others.
2022-10-23 | GSE210116 | GEO
Project description:Chronic viral infections represent a major public health problem. Although it is well understood that neonates and adults respond differently to chronic viral infections (HIV, HCV), the underlying mechanisms remain poorly understood. In this study, we transferred neonatal and adult CD8+ T cells into a mouse model of chronic infection (LCMV clone 13) and dissected out the key cell-intrinsic differences that alter their ability to protect the host. Interestingly, we found that neonatal CD8+ T cells preferentially become effector cells early in chronic infection when compared to adult CD8+ T cells, and resist commitment to the exhausted differentiation trajectory. Further, neonatal CD8+ T cells are preferentially maintained as stem-like exhausted progenitors rather than terminally exhausted cells during the chronic phase of infection. The altered differentiation trajectories of neonatal and adult CD8+ T cells is functionally significant, for the neonatal cells protect from viral replication. Together, our work demonstrates how cell-intrinsic differences between neonatal and adult CD8+ T cells influences key cell fate decisions during chronic infection.
2024-03-07 | GSE234303 | GEO
Project description:Chronic viral infections represent a major public health problem. Although it is well understood that neonates and adults respond differently to chronic viral infections (HIV, HCV), the underlying mechanisms remain poorly understood. In this study, we transferred neonatal and adult CD8+ T cells into a mouse model of chronic infection (LCMV clone 13) and dissected out the key cell-intrinsic differences that alter their ability to protect the host. Interestingly, we found that neonatal CD8+ T cells preferentially become effector cells early in chronic infection when compared to adult CD8+ T cells, and resist commitment to the exhausted differentiation trajectory. Further, neonatal CD8+ T cells are preferentially maintained as stem-like exhausted progenitors rather than terminally exhausted cells during the chronic phase of infection. The altered differentiation trajectories of neonatal and adult CD8+ T cells is functionally significant, for the neonatal cells protect from viral replication at the cost of early-onset immunopathology. Together, our work demonstrates how cell-intrinsic differences between neonatal and adult CD8+ T cells influences key cell fate decisions during chronic infection.
2024-03-07 | GSE234302 | GEO
Project description:Splenic LCMV-specific B cells in acute versus chronic LCMV infection
| PRJNA947097 | ENA
Project description:Chronic viral infection results in CD8 T cell exhaustion. Here, we use paired single-cell RNA sequencing (scRNA-seq) and single-cell T cell receptor sequencing (scTCR-seq) to investigate CD8 T cell phenotypic and clonal heterogeneity in multiple mice during the late stage of LCMV Clone 13 infection.
2022-10-23 | GSE206230 | GEO
Project description:Altered CD8 T cell differentiation and functional exhaustion prevent control of chronic virus infection and cancer. Yet, how fate commitment and exhaustion are determined and dynamically modulated throughout persistent infection are unclear. We compared the activation and differentiation of LCMV GP33-specific CD8 TCR transgenic cells (P14) primed at the onset versus in the midst of established persistent LCMV-Clone 13 viral infection. LCMV GP33-specific CD8 TCR transgenic (P14) cells were injected into naïve mice immediately infected with LCMV-Cl13 (Early priming) or into mice that had been infected 21 days earlier with LCMV-Cl13 (Late Priming). Sixty hours post-priming P14 cells were sorted from mice and subjected to RNA seq. We show early primed cells very rapidly exhibit a transcriptional profile of robust activation, effector differentiation and dysfunction, while late primed cells have increased expression of genes involved in memory differentiation and maintenance.
2018-10-09 | GSE105044 | GEO
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
2012-11-23 | E-GEOD-41867 | biostudies-arrayexpress