A Rapid Translational Immune Response Program in CD8 Memory T Lymphocytes.

Details

Serval ID
serval:BIB_57B92BF0DB50
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A Rapid Translational Immune Response Program in CD8 Memory T Lymphocytes.
Journal
Journal of immunology
Author(s)
Salloum D., Singh K., Davidson N.R., Cao L., Kuo D., Sanghvi V.R., Jiang M., Lafoz M.T., Viale A., Ratsch G., Wendel H.G.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Publication state
Published
Issued date
15/09/2022
Peer-reviewed
Oui
Volume
209
Number
6
Pages
1189-1199
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The activation of memory T cells is a very rapid and concerted cellular response that requires coordination between cellular processes in different compartments and on different time scales. In this study, we use ribosome profiling and deep RNA sequencing to define the acute mRNA translation changes in CD8 memory T cells following initial activation events. We find that initial translation enables subsequent events of human and mouse T cell activation and expansion. Briefly, early events in the activation of Ag-experienced CD8 T cells are insensitive to transcriptional blockade with actinomycin D, and instead depend on the translation of pre-existing mRNAs and are blocked by cycloheximide. Ribosome profiling identifies ∼92 mRNAs that are recruited into ribosomes following CD8 T cell stimulation. These mRNAs typically have structured GC and pyrimidine-rich 5' untranslated regions and they encode key regulators of T cell activation and proliferation such as Notch1, Ifngr1, Il2rb, and serine metabolism enzymes Psat1 and Shmt2 (serine hydroxymethyltransferase 2), as well as translation factors eEF1a1 (eukaryotic elongation factor α1) and eEF2 (eukaryotic elongation factor 2). The increased production of receptors of IL-2 and IFN-γ precedes the activation of gene expression and augments cellular signals and T cell activation. Taken together, we identify an early RNA translation program that acts in a feed-forward manner to enable the rapid and dramatic process of CD8 memory T cell expansion and activation.
Keywords
5' Untranslated Regions, Animals, CD8-Positive T-Lymphocytes, Cycloheximide/metabolism, Dactinomycin/metabolism, Glycine Hydroxymethyltransferase/genetics, Glycine Hydroxymethyltransferase/metabolism, Humans, Immunologic Memory, Interleukin-2/metabolism, Lymphocyte Activation, Memory T Cells, Mice, Peptide Elongation Factor 2/genetics, Peptide Elongation Factor 2/metabolism, Peptide Elongation Factors/genetics, Pyrimidines/metabolism, RNA, Messenger/genetics, Serine/genetics
Pubmed
Web of science
Open Access
Yes
Create date
29/08/2022 8:30
Last modification date
07/10/2023 5:57
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