What are exhausted t cells?
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Exhausted T cells refer to a state of T-cell dysfunction characterized by reduced effector functions and increased expression of inhibitory receptors. This exhaustion can arise from prolonged antigen exposure in chronic viral infections, cancer, and immune-mediated inflammatory diseases, leading to T cells losing their effector functions and memory characteristics. Exhausted T cells, particularly CD8+ T cells, exhibit impaired proliferative and cytotoxic capacities, along with elevated expression of co-inhibitory receptors, impacting their ability to combat tumors effectively. Strategies to reinvigorate exhausted T cells in the tumor microenvironment include immune checkpoint blockade, transcription factor-based therapy, epigenetic therapy, metabolism-based therapy, and cytokine therapy, aiming to enhance anti-tumor immunity and improve clinical outcomes. Understanding and targeting exhausted T cells are crucial in advancing cancer immunotherapy and potentially treating immune-mediated inflammatory diseases.
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| Papers (5) | Insight |
|---|---|
7 Citations | Exhausted T cells in the tumor microenvironment are dysfunctional effector T cells with reduced cytokine secretion and increased inhibitory receptor expression, such as PD-1, impacting antitumor immune responses. |
| Exhausted T-cells lose effector function and memory T-cell characteristics due to prolonged stimulation, observed in chronic infections, cancer, and autoimmune diseases like IMIDs, showing potential for immunotherapy. | |
| Exhausted CD8+ T cells (CD8+ TEXs) are dysfunctional T cells in the tumor microenvironment with impaired function and increased expression of co-inhibitory receptors, impacting anti-tumor immunity. | |
| Exhausted T cells are hypo-responsive cells resulting from chronic antigen exposure in viral infections or cancer, characterized by unclear molecular definition and inconsistent surface receptor reliance in research. | |
1 Citations | Exhausted T cells are a subset of T cells that undergo dysfunction due to prolonged antigen exposure, impacting cancer-immunity cycles and potentially transitioning from assets to liabilities in tumor surveillance. |
Related Questions
How cd8 involved in exhausted T cell through Intestinal immune network for IgA production?5 answersCD8+ T cells play a crucial role in the context of exhausted T cells within the intestinal immune network for IgA production. Exhausted CD8+ T cells are characterized by a loss of effector functions and the expression of inhibitory receptors, impacting immune responses against chronic infections or cancer. In the setting of autoimmune diseases like Celiac disease, a subset of CD8 T cells with regulatory properties, known as CD8 Tregs, can be activated through the T cell receptor to eliminate pathogenic CD4 T cells, contributing to immune regulation. Additionally, in colorectal cancer, pre-exhausted T cells express specific biomarkers like CCT6A and TUBA1B, which are associated with T cell exhaustion and overall patient survival, highlighting the complexity of T cell exhaustion mechanisms in cancer immunotherapy.
Can ebv lead to t cell exhaustion?5 answersEBV (Epstein-Barr virus) infection can indeed lead to T cell exhaustion. Studies have shown that patients with activated PI3Kδ syndrome (APDS), caused by gain-of-function mutations in PI3Kδ, experience impaired immune responses, including T cell exhaustion. This exhaustion is characterized by increased expression of inhibitory receptors like PD-1 on CD8+ T cells, similar to what is observed in HIV patients. Furthermore, inhibition of PD-1 on EBV-specific CD8+ T cells from APDS patients has been shown to enhance their proliferation and effector cytokine production, indicating a potential therapeutic approach to alleviate T cell exhaustion. Therefore, EBV infection, especially in conditions like APDS, can contribute to T cell exhaustion, highlighting the importance of understanding and addressing this phenomenon in the context of viral infections like COVID-19.
What are the relationships between T cell exhaustion and immune regulation?4 answersT cell exhaustion is a state of T cell dysfunction that occurs during chronic infections and tumor progression. It is characterized by low effector function, high expression of inhibitory receptors, unique metabolic patterns, and altered transcriptional profiles. The epigenetic changes associated with exhaustion are distinct from those seen in effector and memory cell differentiation. T cell exhaustion is driven by environmental signals that promote epigenetic modifications, leading to a trajectory towards a dysfunctional state. Factors such as antigen stimulation signal strength, cytokines, and epigenetics play a role in T cell exhaustion. The interaction between immune T cells and other tumor infiltrating cells or inflammatory cytokines in the tumor microenvironment also affects T cell exhaustion. Understanding and interfering with the regulatory mechanisms associated with T cell exhaustion has implications for immunotherapy.
What mechanisms contribute to T cell exhaustion in human diseases?5 answersT cell exhaustion in human diseases is driven by various mechanisms. A transcriptome analysis revealed an overlap of upregulated and downregulated genes in exhausted CD8+ T cells, which were enriched in exhaustion response-related pathways. The emergence of inhibitory receptors, such as programmed cell death protein-1 (PD-1), on CD8+ T cells is a leading cause of exhaustion. Additionally, the expression of inhibitory receptors and transcription factors, including PD-1, TIM3, TOX, and BLIMP1, is upregulated in exhausted Tregs. Imbalance between inhibitory and stimulatory signals, reprogramming of metabolism, and high levels of inhibitory receptors like PD-1, CTLA-4, TIM-3, and Lag-3 contribute to T cell exhaustion in chronic infections and cancer. Furthermore, Thymocyte selection-associated high mobility group box protein (TOX) genes and TOX-associated pathways play a critical role in driving T cell exhaustion in chronic infection and cancer.
Are CMV-specific T cells exhausted in chronic infection?5 answersCMV-specific T cells are not specifically mentioned in the abstracts provided.
What are the mechanisms of CMV-specific T cell exhaustion?3 answersT cell exhaustion in chronic viral infections is driven by factors such as high viral titers, strong TCR stimulation, and high antigen concentrations associated with strong inflammatory signals. The presence or absence of a microbiome does not influence the progression of T cell exhaustion in chronic lymphocytic choriomeningitis virus (LCMV) infections. However, the absence of the microbiome delays the partial viral control typically seen in chronic LCMV infections, indicating that the microbiome is critical for effector T cell function. Non-coding RNAs, including microRNAs and long non-coding RNAs, have been shown to participate in the regulation of T cell exhaustion during chronic viral infections. In chronic hepatitis B and C virus infections, persistently elevated antigen levels drive CD8+ T cells towards a state of exhaustion, which is associated with metabolic and signaling deregulations, as well as epigenetic alterations.