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Immunity. 2017 Mar 21;46(3):364-378. doi: 10.1016/j.immuni.2017.03.010.

Successful and Maladaptive T Cell Aging.

Author information

1
Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Palo Alto Veterans Administration Health Care System, Palo Alto, CA 94304, USA. Electronic address: jgoronzy@stanford.edu.
2
Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Palo Alto Veterans Administration Health Care System, Palo Alto, CA 94304, USA. Electronic address: cweyand@stanford.edu.

Abstract

Throughout life, the T cell system adapts to shifting resources and demands, resulting in a fundamentally restructured immune system in older individuals. Here we review the cellular and molecular features of an aged immune system and discuss the trade-offs inherent to these adaptive mechanisms. Processes include homeostatic proliferation that maintains compartment size at the expense of partial loss in stemness and incomplete differentiation and the activation of negative regulatory programs, which constrain effector T cell expansion and prevent increasing oligoclonality but also interfere with memory cell generation. We propose that immune failure occurs when adaptive strategies developed by the aging T cell system fail and also discuss how, in some settings, the programs associated with T cell aging culminates in a maladaptive response that directly contributes to chronic inflammatory disease.

PMID:
28329703
PMCID:
PMC5433436
DOI:
10.1016/j.immuni.2017.03.010
[Indexed for MEDLINE]
Free PMC Article

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