Regulation of T-cell progenitor survival and cell-cycle entry by the pre-T-cell receptor.
Pre-T-cell receptor (pre-TCR) functions and the study of early thymocyte development continue to fascinate immunologists more than 10 years after the first description and cloning of the receptor. Although multiple reports have addressed several aspects of pre-TCR signaling and function, its ability to regulate diverse functions, including proliferation, survival, and allelic exclusion of the TCR-beta locus, remains an open question. What fascinates us is its central role in the fine balance between physiological differentiation and thymocyte transformation that leads to T-cell leukemia and lymphomas. In this review, we integrate pre-TCR signaling pathways and study their effects on the regulation of T-cell progenitor cell-cycle entry and cell survival. We also connect aberrant pre-TCR signaling to deregulated proliferation and apoptotic balances and thymocyte transformation.
Aifantis
Iannis
I
University of Chicago, Department of Medicine, Section of Rheumatology, Committees of Immunology, Cancer and Developmental Biology, Chicago, IL 60637, USA. iaifantis@medicine.bsd.uchicago.edu
Mandal
Malay
M
Sawai
Katie
K
Ferrando
Adolfo
A
Vilimas
Tomas
T
D000818:Animals; D002453:Cell Cycle; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism
D016693:Receptors, Antigen, T-Cell, alpha-beta