positive regulation of activated T cell autonomous cell death

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of activated T cell autonomous cell death. [GOC:add, GOC:mtg_apoptosis, ISBN:0781765196]

Positive regulation of activated T cell autonomous cell death is a tightly controlled biological process that ensures the elimination of activated T cells once their function is no longer required or when they become harmful. This process is essential for maintaining immune homeostasis and preventing autoimmune diseases. Here's a detailed description:

**1. Activation of T cells:** T cell activation occurs when antigen-presenting cells (APCs), such as dendritic cells, present antigens to T cells via the MHC-peptide complex. This interaction triggers signaling pathways that activate T cells, leading to their proliferation and differentiation into effector T cells.

**2. Induction of apoptosis:** Once T cells are activated, they are susceptible to apoptosis, a programmed cell death process. This sensitivity is a critical mechanism to prevent prolonged immune responses and potential damage to healthy tissues. Several pathways can trigger apoptosis in activated T cells:

**a. Withdrawal of survival signals:** During T cell activation, survival signals are provided by cytokines like IL-2. When these signals are withdrawn, T cells become susceptible to apoptosis.
**b. Fas-FasL interaction:** Activated T cells express the Fas receptor (CD95) on their surface. Upon interaction with its ligand, FasL, expressed on other immune cells like activated T cells or NK cells, a signaling cascade is initiated, leading to caspase activation and apoptosis.
**c. TNF-α pathway:** Tumor necrosis factor-alpha (TNF-α) is a pro-inflammatory cytokine that can induce apoptosis in activated T cells. TNF-α binds to its receptor, TNFR1, on T cells, triggering a signaling pathway that results in caspase activation and apoptosis.
**d. Granzyme B:** Cytotoxic T lymphocytes (CTLs) release granzyme B, a serine protease, which enters target cells through perforin pores. Granzyme B cleaves and activates caspase enzymes, ultimately leading to apoptosis.

**3. Role of regulatory T cells (Tregs):** Tregs play a crucial role in regulating T cell activation and apoptosis. Tregs express the inhibitory molecule CTLA-4, which binds to CD80/CD86 on APCs and inhibits T cell activation and proliferation. Tregs also produce cytokines like IL-10 and TGF-β, which suppress T cell activation and induce apoptosis.

**4. Importance of positive regulation of activated T cell autonomous cell death:**

**a. Maintaining immune homeostasis:** Apoptosis of activated T cells is essential for preventing excessive immune responses and maintaining balance in the immune system.
**b. Preventing autoimmune diseases:** Dysregulation of T cell apoptosis can lead to the accumulation of autoreactive T cells, increasing the risk of autoimmune disorders.
**c. Controlling inflammatory responses:** Apoptosis of activated T cells helps to control inflammation and prevent tissue damage.
**d. Eliminating exhausted T cells:** Exhausted T cells are T cells that have been chronically exposed to antigen and have lost their effector functions. Apoptosis of exhausted T cells allows for the replacement with new, functional T cells.

**5. Therapeutic implications:**

**a. Cancer immunotherapy:** Understanding T cell apoptosis mechanisms can inform the development of therapies that enhance T cell survival and antitumor activity.
**b. Autoimmune disease treatment:** Therapies that target specific pathways involved in T cell apoptosis can potentially control autoimmune disease by eliminating autoreactive T cells.

**In conclusion, the positive regulation of activated T cell autonomous cell death is a vital process that ensures proper immune function and prevents harmful immune responses. Its dysregulation is implicated in various immune disorders, making it an important target for therapeutic interventions.**'
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Proteins (1)

Compounds (7)