THE TROPHIC ACTION OF IL-7 ON PRO-T CELLS - INHIBITION OF APOPTOSIS OF PRO-T1, PRO-T2, AND PRO-T3 CELLS CORRELATES WITH BCL-2 AND BAX LEVELS AND IS INDEPENDENT OF FAS AND P53 PATHWAYS

Signals from the IL-7R are essential for normal thymocyte development. We isolated thymocytes from early developmental stages and observed t hat suspensions of pro-T1, -T2, and -T3 cells rapidly died in culture. Addition of IL-7 promoted their survival, but did not induce cell div ision. Pro-T4 cells did not undergo rapid cell death, and their surviv al was therefore independent of IL-7, Death in the absence of IL-7 sho wed the hallmarks of apoptosis, including DNA fragmentation and annexi n V binding; however, caspase inhibitors blocked DNA fragmentation, bu t did not block cell death. The trophic effect of IL-7 was partially i nhibited by blocking protein synthesis. The p53 pathway was not involv ed in this death pathway, since pro-T cells from p53(-/-) mice also un derwent cell death in the absence of IL-7, The Fas/Fas ligand pathway was not involved in cell death, since Fas-deficient pro-T cells died n ormally in the absence of IL-7, anti-Fas Abs did not protect cells fro m death in the absence of IL-7, and Fas expression was undetectable on cells at these stages. The IL-7 trophic affect correlated with increa sed intracellular levels of Bcl-2 and decreased levels of Bar, whereas no Bcl-X-L, Bcl-w, or Bad was detectable. Thus, maintaining a favorab le Bcl-2/Bax ratio may account for the trophic action of IL-7.