TY - JOUR
T1 - A Rapid Translational Immune Response Program in CD8 Memory T Lymphocytes
AU - Salloum, Darin
AU - Singh, Kamini
AU - Davidson, Natalie R.
AU - Cao, Linlin
AU - Kuo, David
AU - Sanghvi, Viraj R.
AU - Jiang, Man
AU - Lafoz, Maria Tello
AU - Viale, Agnes
AU - Ratsch, Gunnar
AU - Wendel, Hans Guido
N1 - Publisher Copyright:
Copyright © 2022 by The American Association of Immunologists, Inc. All rights reserved.
PY - 2022/9/15
Y1 - 2022/9/15
N2 - 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 59 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 a1) and eEF2 (eukaryotic elongation factor 2). The increased production of receptors of IL-2 and IFN-g 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.
AB - 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 59 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 a1) and eEF2 (eukaryotic elongation factor 2). The increased production of receptors of IL-2 and IFN-g 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.
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U2 - 10.4049/jimmunol.2100537
DO - 10.4049/jimmunol.2100537
M3 - Article
C2 - 36002234
AN - SCOPUS:85138460068
SN - 0022-1767
VL - 209
SP - 1189
EP - 1199
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -