T cell differentiation

Definition

Target type: biologicalprocess

The process in which a precursor cell type acquires characteristics of a more mature T-cell. A T cell is a type of lymphocyte whose definin characteristic is the expression of a T cell receptor complex. [GO_REF:0000022, GOC:jid, GOC:mah]

T cell differentiation is a complex and tightly regulated process that involves a series of developmental stages, starting with hematopoietic stem cells (HSCs) in the bone marrow and culminating in mature, functional T cells in the thymus. This process is essential for the adaptive immune system to effectively recognize and respond to a wide range of pathogens.

**1. Commitment to the T Cell Lineage:**
- HSCs give rise to multipotent progenitors (MPPs), which can differentiate into various blood cell types.
- MPPs further differentiate into common lymphoid progenitors (CLPs), which are committed to the lymphoid lineage.
- CLPs then commit to the T cell lineage, becoming early T cell progenitors (ETPs).

**2. Migration to the Thymus:**
- ETPs migrate from the bone marrow to the thymus, a specialized organ where T cell development takes place.
- The thymus provides a unique microenvironment with specific signaling molecules and cell interactions that are crucial for T cell differentiation.

**3. Double-Negative (DN) Stages:**
- Upon entering the thymus, ETPs are known as double-negative (DN) cells because they lack both CD4 and CD8 coreceptors.
- DN cells progress through four stages (DN1-DN4), each characterized by specific gene expression profiles and interactions with stromal cells.
- During these stages, T cell receptor (TCR) genes undergo rearrangements, generating a diverse repertoire of TCRs.
- TCRs are responsible for recognizing and binding to specific antigens.

**4. Double-Positive (DP) Stage:**
- DN4 cells express both CD4 and CD8 coreceptors, becoming double-positive (DP) cells.
- DP cells undergo positive selection, a process where TCRs with the ability to bind to self-MHC molecules survive and proliferate.
- This ensures that mature T cells can recognize and respond to antigens presented by self-MHC molecules.

**5. Single-Positive (SP) Stage:**
- DP cells that pass positive selection undergo negative selection, a process where TCRs with high affinity for self-antigens are eliminated.
- This prevents autoimmunity, where the immune system attacks its own tissues.
- Following negative selection, DP cells differentiate into either CD4+ or CD8+ single-positive (SP) cells, depending on the specific TCR they express.

**6. Mature T Cells:**
- SP cells leave the thymus as mature, functional T cells, ready to respond to foreign antigens.
- CD4+ T cells (helper T cells) primarily assist other immune cells in fighting infections.
- CD8+ T cells (cytotoxic T cells) directly kill infected cells or cancer cells.

**7. Peripheral T Cell Homeostasis:**
- Mature T cells circulate in the peripheral blood and lymph nodes, constantly monitoring for signs of infection or disease.
- Upon encountering their specific antigen, T cells become activated and proliferate, forming effector T cells.
- Effector T cells mount an immune response to eliminate the threat, while memory T cells are generated for long-term immunity.

**8. T Cell Subsets:**
- CD4+ T cells can further differentiate into various subsets, each with specialized functions:
- Th1 cells: Produce interferon-gamma (IFN-γ) and mediate cell-mediated immunity.
- Th2 cells: Produce IL-4, IL-5, and IL-13, and mediate humoral immunity.
- Th17 cells: Produce IL-17 and IL-22, and mediate inflammation and tissue repair.
- Regulatory T cells (Tregs): Suppress immune responses and maintain tolerance to self-antigens.

**9. Factors Influencing T Cell Differentiation:**
- T cell differentiation is influenced by a complex interplay of genetic, epigenetic, and environmental factors.
- Cytokines, growth factors, and interactions with stromal cells all play critical roles in shaping T cell development.

**10. Significance of T Cell Differentiation:**
- T cell differentiation is crucial for the establishment and maintenance of a functional adaptive immune system.
- Defects in T cell differentiation can lead to immunodeficiency or autoimmunity.'
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Proteins (15)

Compounds (458)