A rapid translational immune response program in CD8 memory T lymphocytes Journal Article
| Authors: | 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. |
| Article Title: | A rapid translational immune response program in CD8 memory T lymphocytes |
| 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 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. Copyright © 2022 by The American Association of Immunologists, Inc. All rights reserved. |
| Keywords: | controlled study; unclassified drug; genetics; nonhuman; cd8+ t lymphocyte; cd8-positive t-lymphocytes; animal cell; mouse; animal; metabolism; animals; mice; animal tissue; interleukin 2; serine; animal experiment; pyrimidines; lymphocyte activation; immune response; gamma interferon; messenger rna; rna, messenger; 5' untranslated region; dactinomycin; pyrimidine derivative; cell expansion; t lymphocyte activation; immunologic memory; interleukin-2; notch1 receptor; 5' untranslated regions; elongation factor; immunological memory; memory t lymphocyte; interleukin 2 receptor; gamma interferon receptor 1; cycloheximide; amino acid metabolism; peptide elongation factors; humans; human; female; article; glycine hydroxymethyltransferase; memory t cells; elongation factor 2; peptide elongation factor 2; eukaryotic elongation factor 2 |
| Journal Title: | Journal of Immunology |
| Volume: | 209 |
| Issue: | 6 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2022-09-15 |
| Start Page: | 1189 |
| End Page: | 1199 |
| Language: | English |
| DOI: | 10.4049/jimmunol.2100537 |
| PUBMED: | 36002234 |
| PROVIDER: | scopus |
| PMCID: | PMC9492650 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2022 -- Source: Scopus |
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