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PMID: 17723218 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor.

Immunity ·Vol. 27 ·No. 2 ·2007-08-00 ·Pages 281-95

Joshi NS, Cui W, Chandele A, Lee HK, Urso DR, Hagman J, Gapin L, Kaech SM

Abstract

As acute infections resolve, effector CD8(+) T cells differentiate into interleukin-7 receptor(lo) (IL-7R(lo)) short-lived effector cells (SLECs) and IL-7R(hi) memory precursor effector cells (MPECs) capable of generating long-lived memory CD8(+) T cells. By using another SLEC marker, KLRG1, we found that KLRG1(hi) effector cells began appearing early during infection and were committed to downregulating IL-7R. Unlike IL-7R(hi) MPECs, KLRG1(hi) IL-7R(lo) SLECs relied on IL-15, but IL-15 could not sustain their long-term maintenance or homeostatic turnover. The decision between SLEC and MPEC fates was regulated by the amount of inflammatory cytokines (i.e., IL-12) present during T cell priming. According to the amount of inflammation, a gradient of T-bet was created in which high T-bet expression induced SLECs and low expression promoted MPECs. These results elucidate a mechanism by which the innate immune system sets the relative amounts of a lineage-determining transcription factor in activated CD8(+) T cells and, correspondingly, regulates their memory cell potential.

MeSH Terms
Animals Biomarkers/analysis,metabolism CD8-Positive T-Lymphocytes/immunology Cytokines/metabolism Immunologic Memory Infections/immunology,microbiology,virology Inflammation/immunology Interferon-gamma/metabolism Interleukin-12/metabolism Interleukin-15/metabolism Lectins, C-Type Mice Mice, Mutant Strains Receptors, Immunologic/analysis,metabolism Receptors, Interleukin-7/metabolism T-Box Domain Proteins/metabolism
Chemicals
Biomarkers Cytokines Interleukin-15 Klrg1 protein, mouse Lectins, C-Type Receptors, Immunologic Receptors, Interleukin-7 T-Box Domain Proteins T-box transcription factor TBX21 Interleukin-12 Interferon-gamma
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Joshi Nikhil S
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Cui Weiguo
Chandele Anmol
Lee Heung Kyu
Urso David R
Hagman James
Gapin Laurent
Kaech Susan M
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1074-7613
DOI
10.1016/j.immuni.2007.07.010
Published
2007-08-00
Pages
281-95
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2034442
Subset
IM
Grants
NIAID NIH HHS · R01 AI066232-01 · United States
NIAID NIH HHS · R01 AI056322-01 · United States
NIAID NIH HHS · R01 AI 066232-01 · United States
NIAID NIH HHS · R01 AI057485 · United States
NIAID NIH HHS · T32 AI055403 · United States
NIAID NIH HHS · R01 AI056322 · United States
NIAID NIH HHS · R01 AI057485-01 · United States
NIAID NIH HHS · R01 AI054661 · United States
NIAID NIH HHS · P01 AI22295 · United States
NIAID NIH HHS · R01 AI066232 · United States
NIAID NIH HHS · P01 AI022295 · United States
Corrections
CommentIn
PMID: 17723210
External Links
PubMed source DOI: 10.1016/j.immuni.2007.07.010 PMC Full Text View journal details
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