negative regulation of T cell mediated immunity

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate, or extent of T cell mediated immunity. [GOC:add]

Negative regulation of T cell mediated immunity is a complex process that involves a variety of mechanisms to prevent excessive or inappropriate T cell activation, ensuring immune homeostasis and preventing autoimmunity. Key players in this process include regulatory T cells (Tregs), inhibitory receptors on T cells, and various cytokines that modulate T cell responses.

**1. Regulatory T Cells (Tregs):**
- Tregs are a specialized subset of T lymphocytes that actively suppress the activation and effector functions of other T cells.
- They express the transcription factor Foxp3, which is essential for their development and function.
- Tregs exert their suppressive activity through various mechanisms, including:
- **Cytokine production:** Tregs secrete immunosuppressive cytokines like IL-10 and TGF-β, which dampen T cell responses.
- **Cell contact-mediated suppression:** Tregs interact directly with target T cells through the expression of surface molecules like CTLA-4 and CD25, leading to their inactivation.
- **Metabolic modulation:** Tregs can influence the metabolic environment of T cells, promoting a less active state.

**2. Inhibitory Receptors on T Cells:**
- T cell receptors (TCRs) are responsible for recognizing and binding to antigens presented on antigen-presenting cells (APCs).
- However, T cells also express a variety of inhibitory receptors that counterbalance TCR activation signals.
- Examples include:
- **CTLA-4:** Binds to the same ligands as CD28 (a positive co-stimulatory receptor), blocking CD28 signaling and inhibiting T cell activation.
- **PD-1:** Binds to PD-L1 and PD-L2 on APCs, leading to T cell exhaustion and suppression.
- **LAG-3:** Interacts with MHC class II molecules on APCs, suppressing T cell activation.

**3. Cytokines:**
- Cytokines, particularly those with immunosuppressive properties, play a crucial role in regulating T cell responses.
- **IL-10:** Secreted by Tregs and other immune cells, inhibits T cell proliferation and cytokine production.
- **TGF-β:** Promotes Tregs differentiation and inhibits T cell activation.
- **IL-35:** A recently discovered cytokine with potent immunosuppressive effects, inducing T cell suppression.

**4. Other Mechanisms:**
- **Apoptosis:** T cells undergo programmed cell death (apoptosis) when they are no longer needed, preventing excessive immune responses.
- **Metabolic reprogramming:** T cell activation is tightly linked to metabolic changes. Negative regulation can involve shifting T cells to a less metabolically active state, reducing their capacity for activation.
- **Immunological tolerance:** The immune system is able to tolerate certain antigens, preventing immune responses against self-antigens, which is crucial for preventing autoimmunity.

**Disruption of Negative Regulation:**
- Failure of these negative regulatory mechanisms can lead to uncontrolled T cell activation, potentially causing autoimmune diseases, allergies, or inflammatory conditions.
- Conversely, excessive negative regulation can lead to immunosuppression and increased susceptibility to infections.
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