CD70-CD27 interactions provide survival and proliferative signals that regulate T cell receptor-driven activation of human γδ peripheral blood lymphocytes

Ana deBarros, Miguel Chaves-Ferreira, Francisco d'Orey, Julie C. Ribot, Bruno Silva-Santos*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)

Abstract

Human Vγ9Vδ2 T cells are potent anti-tumor lymphocytes that specifically respond to pyrophosphate (phospho-) antigens, which constitute the basis of current γδ T-cell-based immunotherapy strategies. Despite a clear involvement of the TCR, the costimulation requirements of Vγ9Vδ2 T cells remain ill-defined. Here, we show that the expression of the CD27 receptor by the vast majority of Vγ9Vδ2 peripheral blood lymphocytes endows them with enhanced proliferative capacity upon ligation by its unique ligand CD70, a tumor necrosis factor superfamily member expressed on lymphoma B-cells but also on TCR-activated γδ T cells. Moreover, Vγ9Vδ2 T-cell treatment with soluble recombinant CD70 induced calcium signals and increased transcription of anti-apoptotic Bcl2a1 and cell-cycle-promoting Cyclin D2 genes. We further demonstrate that the manipulation of CD70-CD27 interactions significantly impacted on Vγ9Vδ2 T-cell survival, proliferation and cytokine secretion, in both loss-of-function and gain-of-function experiments. Thus, CD27 coreceptor signals strongly promoted the expansion of Th1-biased, CD27+ Vγ9Vδ2 peripheral blood lymphocytes in the context of TCR-mediated stimulation with phosphoantigens. These data collectively establish a novel role for the CD70-CD27 axis in human γδ T-cell activation and hence open new perspectives for its modulation in clinical settings.
Original languageEnglish
Pages (from-to)195-201
Number of pages7
JournalEuropean Journal of Immunology
Volume41
Issue number1
DOIs
Publication statusPublished - 27 Oct 2010
Externally publishedYes

Keywords

  • CD27
  • CD70
  • Costimulation
  • Gd T cells

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