CD4+ T-cell help controls CD8+ T-cell memory via TRAIL-mediated activation-induced cell death

Janssen, Edith M.; Droin, Nathalie M.; Lemmens, Edward E.; Pinkoski, Michael J.; Bensinger, Steven J.; Ehst, Benjamin D.; Griffith, Thomas S.; Green, Douglas R.; Schoenberger, Stephen P.

doi:10.1038/nature03337

Cited by 619T-cell and B-cell ImmunologyImmunotherapy and Immune ResponsesImmune responses and vaccinations

CD4+ T-cell help controls CD8+ T-cell memory via TRAIL-mediated activation-induced cell death

Janssen, Edith M., Droin, Nathalie M., Lemmens, Edward E., Pinkoski, Michael J., Bensinger, Steven J., Ehst, Benjamin D., Griffith, Thomas S., Green, Douglas R. +1 more·2005·Nature

DOI 10.1038/nature03337

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Abstract

The 'help' provided by CD4+ T lymphocytes during the priming of CD8+ T lymphocytes confers a key feature of immune memory: the capacity for autonomous secondary expansion following re-encounter with antigen. Once primed in the presence of CD4+ T cells, 'helped' CD8+ T cells acquire the ability to undergo a second round of clonal expansion upon restimulation in the absence of T-cell help. 'Helpless' CD8+ T cells that are primed in the absence of CD4+ T cells, in contrast, can mediate effector functions such as cytotoxicity and cytokine secretion upon restimulation, but do not undergo a second round of clonal expansion. These disparate responses have features of being 'programmed', that is, guided by signals that are transmitted to naive CD8+ T cells during priming, which encode specific fates for their clonal progeny. Here we explore the instructional programme that governs the secondary response of CD8+ T cells and find that helpless cells undergo death by activation-induced cell death upon secondary stimulation. This death is mediated by tumour-necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). Regulation of Trail expression can therefore account for the role of CD4+ T cells in the generation of CD8+ T cell memory and represents a novel mechanism for controlling adaptive immune responses.

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Without licensing signal, activated helpless CTLs function as primary effector T cells but have a short lifespan or die via activation-induced cell death after subsequent antigen exposure.
“Without this additional signal, the activated ‘helpless’ CTL function as primary effector T cells but with a short lifespan69 or die via activation-induced cell death following subsequent exposure to antigen70,71.”
From Immunogenic and tolerogenic cell death (2009) · cites this paper as [71]

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Authors: Janssen, E. M., Droin, N. M., Lemmens, E. E., Pinkoski, M. J., Bensinger, S. J., Ehst, B. D., Griffith, T. S., Green, D. R., & Schoenberger, S. P.
Affiliations: La Jolla Institute for Immunology (US)
University of Minnesota (US)
University of Iowa (US)
Corresponding author: Green, Douglas R.
Schoenberger, Stephen P.
ORCID: Janssen, Edith M.
Droin, Nathalie M.
Lemmens, Edward E.
Bensinger, Steven J.
Ehst, Benjamin D.
Griffith, Thomas S.
Green, Douglas R.
Schoenberger, Stephen P.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2005-03
Volume: 434
Issue: 7029
Pages: 88-93
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature03337
OpenAlex: W1986222655
Cited by: 619
References: 27
Citations by year: 2026: 4 · 2025: 16 · 2024: 19 · 2023: 18 · 2022: 9 · 2021: 15 · 2020: 20 · 2019: 28 · 2018: 14 · 2017: 18 · 2016: 15 · 2015: 27 · 2014: 18 · 2013: 38 · 2012: 33
FWCI: 20.69
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: American Cancer Society
National Institutes of Health
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords: CD4+ T cell help, CD8+ T cell memory, TRAIL, activation-induced cell death, apoptosis, T cell priming, programmed cell death, tumor necrosis factor-related apoptosis-inducing ligand
MeSH terms: Animals, Cells, Cultured, Immunologic Memory, Lymphocyte Activation, Membrane Glycoproteins, RNA, Messenger, Tumor Necrosis Factor-alpha, CD4-Positive T-Lymphocytes, Apoptosis, CD8-Positive T-Lymphocytes, Caspases, Apoptosis Regulatory Proteins, Mice, TNF-Related Apoptosis-Inducing Ligand, Caspase Inhibitors

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CD4+ T-cell help controls CD8+ T-cell memory via TRAIL-mediated activation-induced cell death

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