T cell exhaustion

Definition

T cell exhaustion is a state of dysfunction that occurs in T cells after prolonged exposure to antigens, particularly in the context of chronic infections or cancers. This state is characterized by diminished T cell responses, including reduced cytokine production and impaired proliferation, which can hinder the immune system's ability to effectively eliminate pathogens or cancer cells. Understanding this concept is crucial for grasping how viruses evade the immune system and persist in the host.

5 Must Know Facts For Your Next Test

1. T cell exhaustion typically manifests during chronic infections, such as HIV or hepatitis C, where T cells are continuously exposed to high levels of viral antigens.
2. Exhausted T cells express high levels of inhibitory receptors like PD-1 and CTLA-4, which dampen their activation and function.
3. The process of T cell exhaustion is reversible under certain conditions, particularly with the use of immune checkpoint inhibitors that block inhibitory signals.
4. During T cell exhaustion, there is often a shift in the expression of transcription factors, leading to changes in T cell metabolism and functionality.
5. Understanding T cell exhaustion has important implications for vaccine development and cancer immunotherapy strategies aimed at reactivating exhausted T cells.

Review Questions

• How does T cell exhaustion affect the immune response during chronic infections?
  • T cell exhaustion significantly impairs the immune response by reducing the ability of T cells to proliferate and produce cytokines, which are essential for mounting an effective attack against pathogens. In chronic infections, persistent exposure to viral antigens leads to this dysfunction, resulting in inadequate clearance of the virus. Consequently, the body struggles to control the infection, allowing it to persist and potentially progress.
• What role do inhibitory receptors play in the development of T cell exhaustion?
  • Inhibitory receptors such as PD-1 and CTLA-4 play a critical role in the development of T cell exhaustion by sending negative signals that reduce T cell activation and proliferation. When these receptors are overexpressed on T cells exposed to chronic antigen stimulation, they lead to a functional decline in T cells. Targeting these pathways with immune checkpoint inhibitors can help reverse exhaustion and restore effective T cell responses.
• Evaluate the potential therapeutic strategies for overcoming T cell exhaustion in chronic infections and cancer.
  • Overcoming T cell exhaustion involves several therapeutic strategies, including the use of immune checkpoint inhibitors that block inhibitory receptors like PD-1. These agents have shown promise in enhancing T cell activity against tumors and chronic infections by reversing the exhausted state. Additionally, combination therapies that include vaccines or cytokine therapy aim to boost overall immune responses while also re-engaging exhausted T cells. Research into metabolic reprogramming of exhausted T cells also holds potential for developing innovative treatments to revive their functionality.

Related terms

Cytokine: Signaling molecules that mediate and regulate immunity, inflammation, and hematopoiesis, playing a vital role in the immune response.

Immune checkpoint inhibitors: Therapeutic agents that block inhibitory pathways in the immune system, enhancing T cell activity against tumors.

Chronic infection: An infection that persists over time, often leading to a continuous antigenic stimulus and potential T cell exhaustion.