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- Title
CD4<sup>+</sup> T-cell help controls CD8<sup>+</sup> T-cell memory via TRAIL-mediated activation-induced cell death.
- Authors
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.
- 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.
- Publication
Nature, 2005, Vol 434, Issue 7029, p88
- ISSN
0028-0836
- Publication type
Academic Journal
- DOI
10.1038/nature03337