Natural Tregs arise in the thymus Thymus Aire+ mTEC Thymocyte Treg
Natural Tregs arise in the thymus
Aire + mTEC Thymocyte 2° Signal LAT Foxp3 NFAT: Foxp3: DNA NFKB Ag: TCR MHC Figure 2 Lineage commitment of the natural Treg. In the thymus, developing thymocytes interact with Aire+ medullary thymic epithelial cells presenting tissue-specific self-antigens in the context of their MHC molecules. The combination of a high-affinity TCR interaction with the self-peptide: MHC complex along with secondary signals, such as CD28 engagement, direct Treg lineage commitment in the thymus. These interactions drive a Treg-specific signaling cascade which upregulates Foxp3 gene expression The resultant Foxp3 protein can form a cooperative complex with NFAT on DNA, acting as a transcription factor to both repress genes involved in T-cell activation, such as IL-2 and IL-4, and activate those required for the treg genetic program, such as CD25 and CTLA-4
T Lymphocyte Tolerance O Central Cell Tolerance o Peripheral T cell Tolerance
T Lymphocyte Tolerance ⚫ Central T Cell Tolerance ⚫ Peripheral T cell Tolerance
Peripheral T cell Tolerance o Antigen recognition without adequate costimulation o Use ctla-4 to recognize costimulators on APCs O Activation induced cell death(AICD) o Regulatory T Lymphocytes o Factors that determine the tolerogenicity of self antigens
Peripheral T cell Tolerance ⚫ Antigen recognition without adequate costimulation ⚫ Use CTLA-4 to recognize costimulators on APCs ⚫ Activation induced cell death (AICD) ⚫ Regulatory T Lymphocytes ⚫ Factors that determine the tolerogenicity of self antigens
Peripheral T cell Tolerance o Antigen recognition without adequate costimulation O Use CTLA-4 to recognize costimulators on APCS ●A|CD Treg o Factors that determine the tolerogenicity of self antigens
Peripheral T cell Tolerance ⚫ Antigen recognition without adequate costimulation ⚫ Use CTLA-4 to recognize costimulators on APCs ⚫ AICD ⚫ Treg ⚫ Factors that determine the tolerogenicity of self antigens