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

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

Research output: Contribution to journalArticlepeer-review

523 Scopus citations


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 antigen1-4. 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.

Original languageEnglish (US)
Pages (from-to)88-93
Number of pages6
Issue number7029
StatePublished - Mar 3 2005
Externally publishedYes

ASJC Scopus subject areas

  • General


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