The role of Notch and IL-7 signaling in early thymocyte proliferation and differentiation.
We have analyzed the roles of Notch and IL-7 signaling in the proliferation and differentiation of mouse progenitor thymocyte subpopulations cultured on Notch delta-like-1 ligand-expressing OP9 stromal cells. Using bulk and limiting dilution cultures, we show that DN1 and DN2 cells require both Notch and IL-7 signaling for efficient proliferation and differentiation into cytoplasmic TCRbeta and surface TCRalpha/beta and TCRgamma/delta expressing T cells. Selection for cytoplasmic TCRbeta-positive cells is dependent on preTalpha expression. Both gamma/delta and alpha/beta TCR expressing T cells arising in culture can be efficiently stimulated by anti-CD3 cross-linking, suggesting that they might be functional. The differentiation of adult, but not fetal, DN1 and DN2 thymocytes into CD4 and/or CD8 expressing cells is inhibited by IL-7. Finally, efficient proliferation and differentiation of DN3 cells requires Notch signaling and preTCR expression, but is independent of IL-7.
Balciunaite
Gina
G
Developmental and Molecular Immunology, Department of Clinical and Biological Sciences (DKBW), University of Basel, Basel, Switzerland.
Ceredig
Rhodri
R
Fehling
Hans-Jörg
HJ
Zúñiga-Pflücker
Juan-Carlos
JC
Rolink
Antonius G
AG
D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D015321:Gene Rearrangement / Q000235:genetics*; D015851:Interleukin-7 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch; D015398:Signal Transduction / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*
D015851:Interleukin-7; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D051880:Receptors, Notch