T Lymphocyte Development and Differentiation: Key Factors and Mechanisms
T cell development in the thymus is orchestrated by multiple interacting factors:
- Transcription factors (TCF-1, GATA3, FoxO1) control gene expression for lineage specification.
- Cytokines/growth factors (IL-2, IL-4, IL-7, IL-15) from stromal cells drive growth, survival, differentiation.
- Notch signaling directs fate decisions toward CD4+ or CD8+ lineages.
- Pre-TCR mediates transition from double-negative to double-positive stage.
- MHC-TCR interactions enable positive selection (self-MHC recognition) and negative selection (self-tolerance).
- Costimulatory molecules (CD28, ICOS) enhance activation.
- Epigenetic modifications (DNA methylation, histone changes) shape gene accessibility.
- Thymic microenvironment provides extracellular matrix, cytokines, and cellular interactions.
Together, these ensure a diverse, functional T cell repertoire.
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