Beta-catenin signaling mediates CD4 expression on mature CD8+ T cells.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Jason M SchenkelLena Al-Harthi

Abstract

Upon activation, a subset of mature human CD8(+) T cells re-expresses CD4 dimly. This CD4(dim)CD8(bright) T cell population is genuine and enriched in antiviral CD8(+) T cell responses. The signaling pathway that leads to CD4 re-expression on mature CD8(+) T cells is not clear. Given that Wnt/beta-catenin signaling plays a critical role in the transition of CD4(-)CD8(-) to CD4(+)CD8(+) thymocytes, we determined whether beta-catenin mediates CD4 expression on mature CD8(+) T cells. We demonstrate that active beta-catenin expression is 20-fold higher on CD4(dim)CD8(bright) than CD4(-)CD8(+) T cells. Activation of beta-catenin signaling, through LiCl or transfection with a constitutively active construct of beta-catenin, induced CD4 on CD8(+) T cells by approximately 10-fold. Conversely, inhibition of beta-catenin signaling through transfection with a dominant-negative construct for T cell factor-4, a downstream effector of beta-catenin signaling, diminished CD4 expression on CD8(+) T cells by 50% in response to T cell activation. Beta-catenin-mediated induction of CD4 on CD8(+) T cells is transcriptionally regulated, as it induced CD4 mRNA, and T cell factor/lymphoid enhancer factor sites were identified within the human CD4 prom...Continue Reading

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Citations

Sep 20, 2011·Nature Medicine·Luca GattinoniNicholas P Restifo
Jan 7, 2015·Immunopharmacology and Immunotoxicology·Narendra Maddu, Pongali B Raghavendra
Jun 8, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lena Al-Harthi
Sep 23, 2020·PloS One·Amber K VirdiLena Al-Harthi
Nov 20, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maureen H RichardsLena Al-Harthi
Sep 6, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jennillee WallaceLena Al-Harthi
Apr 17, 2016·Kidney International·Babita MadanSteven D Crowley

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