negative regulation of T cell mediated cytotoxicity

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the rate of T cell mediated cytotoxicity. [GOC:add, ISBN:0781735149]

Negative regulation of T cell mediated cytotoxicity is a complex and essential process that prevents excessive immune responses and autoimmune damage. It involves a coordinated interplay of various signaling pathways, inhibitory receptors, and regulatory cells. Here's a detailed breakdown of the process:

**1. Activation and Differentiation of Cytotoxic T lymphocytes (CTLs):**
- CTLs are a subset of T lymphocytes that are primarily responsible for killing infected or cancerous cells.
- Activation of CTLs requires two signals:
- Signal 1: Recognition of antigen presented by MHC class I molecules on target cells by the T cell receptor (TCR) on the CTL.
- Signal 2: Costimulatory signals delivered by molecules like CD28 on the CTL interacting with CD80/CD86 on antigen-presenting cells (APCs).
- Upon activation, CTLs differentiate into effector CTLs capable of mediating cytotoxicity.

**2. Inhibitory Receptors and Signaling Pathways:**
- Negative regulation of CTL activity is crucial to prevent collateral damage to healthy cells and maintain immune homeostasis. This regulation is achieved through various inhibitory receptors expressed on CTLs. Some key examples include:
- **CTLA-4 (Cytotoxic T-Lymphocyte Antigen-4):** CTLA-4 is a powerful negative regulator that binds to CD80/CD86, competing with CD28 for binding. This interaction delivers an inhibitory signal that limits CTL activation and proliferation.
- **PD-1 (Programmed Cell Death Protein 1):** PD-1 is another important inhibitory receptor expressed on CTLs. It binds to PD-L1 and PD-L2 ligands on target cells or APCs. This interaction triggers intracellular signaling pathways leading to suppression of CTL function.
- **LAG-3 (Lymphocyte-Activation Gene 3):** LAG-3 interacts with MHC class II molecules on APCs. Its engagement delivers inhibitory signals that dampen CTL activity.
- **TIM-3 (T-cell Immunoglobulin and Mucin-domain containing 3):** TIM-3 binds to galectin-9 on target cells or APCs, contributing to the suppression of CTL function.
- **BTLA (B and T Lymphocyte Attenuator):** BTLA interacts with HVEM (Herpesvirus Entry Mediator) on APCs, resulting in the suppression of CTL activation.

**3. Regulatory T cells (Tregs):**
- Tregs are specialized T cells that play a vital role in suppressing immune responses, including CTL activity.
- Tregs express the transcription factor Foxp3 and exhibit a unique phenotype characterized by the expression of inhibitory molecules like CTLA-4 and CD25.
- Tregs directly interact with CTLs and other immune cells, releasing immunosuppressive cytokines such as IL-10 and TGF-β. These cytokines inhibit CTL activation, proliferation, and cytotoxicity.

**4. Cytokine Modulation:**
- Cytokines, such as IL-10 and TGF-β, can directly suppress CTL function by modulating signaling pathways involved in CTL activation and effector functions.

**5. Apoptosis of CTLs:**
- CTLs are not immortal cells and can undergo programmed cell death (apoptosis) after activation and effector function. This intrinsic mechanism limits CTL activity over time.

**Overall, the negative regulation of T cell mediated cytotoxicity is a dynamic process that involves multiple layers of control. These mechanisms ensure the proper balance of immune responses, preventing excessive inflammation and autoimmune damage while maintaining the ability to fight infections and cancer.**'
"

Proteins (2)

Compounds (11)