Cell death and thymic tolerance
Details
Publication Year 2017-05, Volume 277, Issue #1, Page 9-20
Journal Title
Immunology Reviews
Publication Type
Journal Article
Abstract
The differentiation of hematopoietic precursors into the many functionally distinct T-cell types produced by the thymus is a complex process. It proceeds through a series of stages orchestrated by a variety of thymic microenvironments that shape the T-cell developmental processes. Numerous cytokine and cell surface receptors direct thymocyte differentiation but the primary determinant of cell fate is the engagement of the T-cell antigen receptor (TCR). The strength of the TCR signal and the maturation stage of the thymocyte receiving it can direct the various differentiation programs or, alternatively, end the process by inducing cell death. The regulation of thymocyte death is critical for the efficiency of thymic T-cell differentiation and the preservation of immune tolerance. A detailed knowledge of mechanisms that eliminate thymocytes from the T-cell repertoire is essential to understand the "logic" of T-cell selection in the thymus. This review focuses on the central role of the BCL-2 family of proteins in the apoptotic checkpoints that punctuate thymocyte differentiation and the consequences of defects in these processes.
Publisher
Wiley
WEHI Research Division(s)
Molecular Genetics Of Cancer
PubMed ID
28462532
Publisher's Version
https://doi.org/10.1111/imr.12532
NHMRC Grants
NHMRC/1089072 NHMRC/1020363 NHMRC/1078763
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2017-05-15 01:16:26
Last Modified: 2018-05-03 08:05:08
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