The role of Notch and IL‐7 signaling in early thymocyte proliferation and differentiation

• Published in: European journal of immunology Vol. 35; no. 4; pp. 1292 - 1300
• Main Authors: Balciunaite, Gina, Ceredig, Rhodri, Fehling, Hans‐Jörg, Zúñiga‐Pflücker, Juan‐Carlos, Rolink, Antonius G.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.04.2005
• Subjects: Cell Differentiation - physiology; Cell Division - physiology; Gene Rearrangement - genetics; IL‐7; Interleukin-7 - metabolism; Lymphopoiesis; Membrane Proteins - metabolism; Notch; preTCR; Progenitor cells; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; Receptors, Notch; Signal Transduction - physiology; Stromal Cells - physiology; Thymus Gland - cytology; Thymus Gland - metabolism
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200425822

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 TCRβ and surface TCRα/β and TCRγ/δ expressing T cells. Selection for cytoplasmic TCRβ‐positive cells is dependent on preTα expression. Both γ/δ and α/β 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.