Document Detail


T-cell memory differentiation: insights from transcriptional signatures and epigenetics.
MedLine Citation:
PMID:  23347146     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A critical component of vaccine design is to generate and maintain antigen-specific memory lymphocytes of sufficient quantity and quality to give the host life-long protection against re-infection. Therefore, it is important to understand how memory T cells acquire the ability for self-renewal while retaining a potential for heightened recall of effector functions. During acute viral infection or following vaccination, antigen-specific T cells undergo extensive phenotypic and functional changes during differentiation to the effector and memory phases of the immune response. The changes in cell phenotype that accompany memory T-cell differentiation are predominantly mediated through acquired transcriptional regulatory mechanisms, in part achieved through epigenetic modifications of DNA and histones. Here we review our current understanding of epigenetic mechanisms regulating the off-on-off expression of CD8 and CD4 T-cell effector molecules at naive, effector and memory stages of differentiation, respectively, and how covalent modifications to the genome may serve as a mechanism to preserve 'poised' transcriptional states in homeostatically dividing memory cells. We discuss the potential of such mechanisms to control genes that undergo on-off-on patterns of expression including homing and pro-survival genes, and the implications on the development of effector-memory and central-memory T-cell differentiation. Lastly, we review recent studies demonstrating epigenetic modifications as a mechanism for the progressive loss of transcriptional adaptation in antigen-specific T cells that undergo sustained high levels of T-cell receptor signalling.
Authors:
Ben Youngblood; J Scott Hale; Rafi Ahmed
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Immunology     Volume:  139     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-14     Completed Date:  2013-08-19     Revised Date:  2014-07-01    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  277-84     Citation Subset:  IM    
Copyright Information:
© 2013 John Wiley & Sons Ltd.
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MeSH Terms
Descriptor/Qualifier:
CD4-Positive T-Lymphocytes / cytology*,  immunology,  metabolism
CD8-Positive T-Lymphocytes / cytology*,  immunology,  metabolism
Cell Differentiation* / genetics,  immunology
Epigenomics*
Gene Expression Regulation
Humans
Immunologic Memory
Lymphocyte Activation
Grant Support
ID/Acronym/Agency:
AHMED05GCGH0//PHS HHS; F32 A1096709-01A1//PHS HHS; F32 AI096709/AI/NIAID NIH HHS; P01 AI080192-01/AI/NIAID NIH HHS; R01 AI030048/AI/NIAID NIH HHS; R37 AI30048-17/AI/NIAID NIH HHS
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