Pathway
Differentiation of T cells
Thymic seeding progenitors (TSPs), originating from the bone marrow, enter the thymus and pass through six double negative (CD4-/CD8-) stages: DN1, DN2a, DN2b, DN3a, DN3b, and DN4 (reviewed in Sun et al. 2023). T cell receptor components are initially expressed in DN3b cells. Double negative 4 (DN4) cells then express both CD4 and CD8 and are designated double positive (DP) cells. DP cells then differentiate into single positive cells: naive (not yet activated by antigen) CD4+ T cells and naive CD8+ T cells.
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Upon stimulation of the T cell receptor (TCR) by antigen, CD4+ T cells are directed by other external factors, notably cytokines, to differentiate into various types of T helper cells. The different types of T helper cells are characterized by master regulatory transcription factors and secreted effector cytokines (reviewed in Lee 2023, Sun et al. 2023):
T helper 1 (Th1) cells are regulated by TBX21 (T-bet) and secrete interferon gamma (IFNG).
T helper 2 (Th2) cells are regulated by GATA3 and secrete IL4, IL5, and IL13.
T helper 9 (Th9) cells are regulated by IRF4 and SPI1 (PU.1) and secrete IL9, IL10, and IL21.
T helper 17 (Th17) cells are regulated by RORC isoform t (RORgammat) and STAT3 (reviewed in Imam et al. 2018) and secrete IL17A, IL17F, and IL22.
T helper 22 (Th22) cells are regulated by TBX21 and STAT3 and secrete IL22, but not IFNG or IL17 (reviewed in Imam et al. 2018).
T follicular helper (Tfh) cells are regulated by BCL6 and secrete IL21.
T regulatory (Treg) cells are regulated by FOXP3 and secrete IL10.
REACT:R-HSA-9945266Reactome
What the reference databases state
Statements
84 statements
84 statements · 1 reference database · Subject: Differentiation of T cells · Sources: Reactome
- ASH2L participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- BATF participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- BMI1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- CBX2 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- CBX4 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- CBX6 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- CBX8 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- CCL3 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- CHD3 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- CHD4 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- CREBBP participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- DPY30 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
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- EP300 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- ETS1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- FOS participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- GATA3 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- GATAD2A participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- GATAD2B participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- HDAC1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- HDAC10 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- HDAC11 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- HDAC2 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- HDAC3 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- HDAC4 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- HDAC5 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- HDAC6 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- HDAC7 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- HDAC8 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- HDAC9 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- IFNG participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- IL12RB2 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- IL13 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- IL4 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- IL4R participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- IL5 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- IRF4 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- JUN participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- KAT2A participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- KAT2B participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- KLF13 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- KMT2A participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- MAF participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- MAML1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- MAML2 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- MAML3 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- MAMLD1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- MBD3 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- MEN1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- MTA1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- MTA2 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- MTA3 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- NCOR1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- NCOR2 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- NFATC1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- NFATC2 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- NOTCH1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- NOTCH2 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- PHC1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- PHC2 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- PHC3 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- POU2F1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- POU2F2 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- RBBP4 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- RBBP5 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- RBBP7 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- RBPJ participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- RING1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- RNF2 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- RUNX1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- RUNX3 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- SATB1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- SMARCA4 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- SNW1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- STAT4 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- STAT5A participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- STAT5B participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- STAT6 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- TBL1X participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- TBL1XR1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- TBX21 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- TNF participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- TPST2 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- WDR5 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only
- YY1 participates in Differentiation of T cellsProteinReactome R-HSA-9945266Inferred only