Abstract
Abstract During the CD4-CD8- double negative (DN) stage of T cell development, the cells express TCRβ for the first time. TCRβ+ cells activate signaling pathways that promote survival, proliferation, and differentiation, but the receptors required for these signals are unknown. While Notch and IL-7 are critical for early T cell development, their function in TCRβ-expressing DN and immature single positive (ISP) CD8+ thymocytes are unclear. Here, we cultured purified DN3E (CD44-CD25hi), DN3L (CD44-CD25lo), DN4 (CD44-CD25-) and ISP CD8+ thymocytes with OP9 cells that express either the Notch ligand Delta-like 1 (DL1) or control protein. To some samples, IL-7 was also added. DN and ISP thymocytes were able to differentiate into CD4+CD8+ double positive (DP) thymocytes independently of Notch and IL-7. However, Notch promoted the proliferation and survival of the thymocytes, whereas IL-7 promoted survival and slowed differentiation. These data demonstrate that Notch and IL-7 continue to function beyond the time at which TCRβ is expressed and regulate survival, proliferation, and differentiation of TCRβ-expressing thymocytes. This research is supported by the America Cancer Society grant RSG-08-182-01-LIB.
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