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PMID: 20619696 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Repetitive antigen stimulation induces stepwise transcriptome diversification but preserves a core signature of memory CD8(+) T cell differentiation.

Immunity ·Vol. 33 ·No. 1 ·2010-07-23 ·Pages 128-40

Wirth TC, Xue HH, Rai D, Sabel JT, Bair T, Harty JT, Badovinac VP

Abstract

Repetitive antigen stimulation by prime-boost vaccination or pathogen reencounter increases memory CD8(+) T cell numbers, but the impact on memory CD8(+) T cell differentiation is unknown. Here we showed that repetitive antigen stimulations induced accumulation of memory CD8(+) T cells with uniform effector memory characteristics. However, genome-wide microarray analyses revealed that each additional antigen challenge resulted in the differential regulation of several hundred new genes in the ensuing memory CD8(+) T cell populations and, therefore, in stepwise diversification of CD8(+) T cell transcriptomes. Thus, primary and repeatedly stimulated (secondary, tertiary, and quaternary) memory CD8(+) T cells differed substantially in their molecular signature while sharing expression of a small group of genes and biological pathways, which may constitute a core signature of memory differentiation. These results reveal the complex regulation of memory CD8(+) T cell differentiation and identify potential new molecular targets to dissect the function of memory cells generated by repeated antigen stimulation.

MeSH Terms
Animals Antigens/genetics,immunology,metabolism CD8-Positive T-Lymphocytes/immunology,metabolism,microbiology,pathology Cell Differentiation Cells, Cultured Gene Expression Profiling Immunization, Secondary Immunologic Memory Immunophenotyping Listeriosis/immunology,microbiology Lymphocyte Subsets/immunology,metabolism,microbiology,pathology Mice Mice, Inbred C57BL Mice, Transgenic Microarray Analysis Ovalbumin/genetics,immunology,metabolism Transgenes/genetics
Chemicals
Antigens Ovalbumin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Wirth Thomas C
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
Xue Hai-Hui
Rai Deepa
Sabel Jaime T
Bair Tom
Harty John T
Badovinac Vladimir P
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2010.06.014
Published
2010-07-23
Epub
2010-00-08
Pages
128-40
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2912220
Subset
IM
Grants
NIAID NIH HHS · R01 AI050073 · United States
NIAID NIH HHS · R01 AI083286 · United States
NIAID NIH HHS · R37 AI042767-10 · United States
NIAID NIH HHS · AI59752 · United States
NIAID NIH HHS · R01 AI042767 · United States
NIAID NIH HHS · AI50073 · United States
NIAID NIH HHS · R01 AI050073-10 · United States
NIAID NIH HHS · R21 AI077504 · United States
NIAID NIH HHS · R01 AI046653 · United States
NIAID NIH HHS · R37 AI042767 · United States
NHLBI NIH HHS · HL095540 · United States
NIAID NIH HHS · R01 AI059752-05 · United States
NIAID NIH HHS · R01 AI046653-09 · United States
NIAID NIH HHS · R01 AI059752 · United States
NIAID NIH HHS · AI077504 · United States
NIAID NIH HHS · AI83286 · United States
NIAID NIH HHS · AI42767 · United States
NHLBI NIH HHS · R01 HL095540 · United States
NIAID NIH HHS · R21 AI042767 · United States
NIAID NIH HHS · AI46653 · United States
External Links
PubMed source DOI: 10.1016/j.immuni.2010.06.014 PMC Full Text View journal details
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