PD-1 Protects Bystander-Activated T Cells from Activation-Induced Cell Death
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA820849 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18507359.fastq.gz | Fastqsanger.gz | |||
| SRR18507360.fastq.gz | Fastqsanger.gz | |||
| SRR18507361.fastq.gz | Fastqsanger.gz | |||
| SRR18507362.fastq.gz | Fastqsanger.gz | |||
| SRR18507363.fastq.gz | Fastqsanger.gz |
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Project description:There is much evidence that T cells may be activated via mechanisms which act independently of direct TCR ligation. Despite this, the question of whether such forms of ‘bystander’ T cell activation occur during immune responses is hotly debated. To address some outstanding questions, we set up an in vitro system within which to analyse bystander T cell activation in human T cells, in the absence of the possibility for TCR cross-reactivity. In addition, we have investigated the genetic, phenotypic, and functional characteristics of bystander activated T cells. Here, we show that bystander T cell activation is, indeed, observed during a specific immune response, and that it occurs preferentially amongst CD4+ memory T cells. Furthermore, bystander activated T cells display a distinct gene expression profile. The mechanism for bystander T cell activation involves soluble factors, and the outcome is an elevated level of apoptosis. This may provide an explanation for the attrition of T cell memory pools of heterologous specificity during immune responses to pathogens such as viruses.
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Project description:There is much evidence that T cells may be activated via mechanisms which act independently of direct TCR ligation. Despite this, the question of whether such forms of âbystanderâ T cell activation occur during immune responses is hotly debated. To address some outstanding questions, we set up an in vitro system within which to analyse bystander T cell activation in human T cells, in the absence of the possibility for TCR cross-reactivity. In addition, we have investigated the genetic, phenotypic, and functional characteristics of bystander activated T cells. Here, we show that bystander T cell activation is, indeed, observed during a specific immune response, and that it occurs preferentially amongst CD4+ memory T cells. Furthermore, bystander activated T cells display a distinct gene expression profile. The mechanism for bystander T cell activation involves soluble factors, and the outcome is an elevated level of apoptosis. This may provide an explanation for the attrition of T cell memory pools of heterologous specificity during immune responses to pathogens such as viruses. Experiment Overall Design: Three conditions tested with 4 biological repilicates in each: Experiment Overall Design: Resting cells - cells expressing a TCR which does not specifically recognize SEB (Vβ13.1 T cells) and did not upregulate the activation marker CD25 in response to transwell SEB-stimulated co-culture over a 5 day period. Experiment Overall Design: Bystander activated cells - cells expressing a TCR which does not specifically recognize SEB (Vβ13.1 T cells), but which did upregulate the activation marker CD25 in response to transwell SEB-stimulated co-culture over a 5 day period. Experiment Overall Design: Directly activated cells - cells expressing a TCR which is known to specifically recognize SEB (Vβ17 T cells), and which did upregulate the activation marker CD25 in response to direct SEB stimulation over a 5 day period.
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