CD4 + T Cell Help Confers a Cytotoxic T Cell Effector Program Including Coinhibitory Receptor Downregulation and Increased Tissue Invasiveness

CD4 T cells optimize the cytotoxic T cell (CTL) response in magnitude and quality, by unknown molecular mechanisms. We here present the transcriptomic changes in CTLs resulting from CD4 T cell help after anti-cancer vaccination or virus infection. The gene expression signatures revealed that CD4 T c...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Vol. 47; no. 5; p. 848
Main Authors: Ahrends, Tomasz, Spanjaard, Aldo, Pilzecker, Bas, Bąbała, Nikolina, Bovens, Astrid, Xiao, Yanling, Jacobs, Heinz, Borst, Jannie
Format: Journal Article
Language:English
Published: United States 21.11.2017
Subjects:
Animals
CD27 Ligand - physiology
CD4-Positive T-Lymphocytes - physiology
Cell Differentiation
Cell Movement
CX3C Chemokine Receptor 1 - physiology
Down-Regulation
Mice
Mice, Inbred C57BL
Receptors, CXCR4 - physiology
T-Lymphocytes, Cytotoxic - immunology
Tumor Necrosis Factor Receptor Superfamily, Member 7 - physiology
CD4 T cell help
CD8 T cell
costimulation
CTL differentiation
transcriptome
migration
coinhibition
tumor immunity
vaccination
virus infection
ISSN:1097-4180, 1097-4180
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Summary:CD4 T cells optimize the cytotoxic T cell (CTL) response in magnitude and quality, by unknown molecular mechanisms. We here present the transcriptomic changes in CTLs resulting from CD4 T cell help after anti-cancer vaccination or virus infection. The gene expression signatures revealed that CD4 T cell help during priming optimized CTLs in expression of cytotoxic effector molecules and many other functions that ensured efficacy of CTLs throughout their life cycle. Key features included downregulation of PD-1 and other coinhibitory receptors that impede CTL activity, and increased motility and migration capacities. "Helped" CTLs acquired chemokine receptors that helped them reach their tumor target tissue and metalloprotease activity that enabled them to invade into tumor tissue. A very large part of the "help" program was instilled in CD8 T cells via CD27 costimulation. The help program thus enhances specific CTL effector functions in response to vaccination or a virus infection.
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ISSN:1097-4180
1097-4180
DOI:10.1016/j.immuni.2017.10.009