A survival guide to early T cell development.
The survival of immature T cell precursors is dependent on both thymus-derived extrinsic signals and self-autonomous pre-TCR-mediated signals. While the role of cytokines and the pre-TCR in promoting thymocyte survival has been well established, the relationship between pro- and anti-apoptotic signaling cascades remains poorly defined. Recent studies have established a link between cell survival and growth factor-mediated maintenance of cellular metabolism. In this regard, the Notch signaling pathway has emerged as more than an inducer of T lineage commitment and differentiation, but also as a potent trophic factor, promoting the survival and metabolic state of pre-T cells. In this review, we describe current concepts of the intracellular signaling pathways downstream of cell intrinsic and extrinsic factors that dictate survival versus death outcomes during early T cell development.
Ciofani
Maria
M
Department of Immunology, University of Toronto, and Sunnybrook and Women's Research Institute, 2075 Bayview Ave., Toronto, Ontario, M4N 3M5 Canada.
Zúñiga-Pflücker
Juan Carlos
JC
D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D019674:Genes, T-Cell Receptor beta; D006801:Humans; D016023:Integrins / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*
D016207:Cytokines; D016023:Integrins; D051880:Receptors, Notch