Immunity
Volume 47, Issue 5, 21 November 2017, Pages 848-861.e5
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Article
CD4+ T Cell Help Confers a Cytotoxic T Cell Effector Program Including Coinhibitory Receptor Downregulation and Increased Tissue Invasiveness

https://doi.org/10.1016/j.immuni.2017.10.009Get rights and content
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Highlights

  • CD4+ T cell help confers a specific CTL effector program

  • Help improves migratory potential and downregulates coninhibitory receptors on CTLs

  • CTLs primed in absence of “help” have impaired anti-tumor activity

  • Help is largely relayed via CD70 on DCs and CD27 on CD8+ T cells

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.

Keywords

CTL differentiation
CD4 T cell help
tumor immunity
transcriptome
migration
coinhibition
costimulation
CD8 T cell
vaccination
virus infection

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