IL-12-Induced Immune Suppressive Deficit During CD8+ T-Cell Differentiation.

Frontiers in Immunology
Pranav S RenavikarNitin J Karandikar

Abstract

Autoimmune diseases are characterized by regulatory deficit in both the CD4+ and CD8+ T-cell compartments. We have shown that CD8+ T-cells associated with acute relapse of multiple sclerosis are significantly deficient in their immune suppressive ability. We hypothesized that distinct CD8+ cytotoxic T-cell (Tc) lineages, determined by cytokine milieu during naïve T-cell differentiation, may harbor differential ability to suppress effector CD4+ T-cells. We differentiated purified human naïve CD8+ T-cells in vitro toward Tc0 (media control), Tc1 and Tc17 lineages. Using in vitro flow cytometric suppression assays, we observed that Tc0 and Tc17 cells had similar suppressive ability. In contrast, Tc1 cells showed significant loss of suppressive ability against ex vivo CD4+ T-cells and in vitro-differentiated Th0, Th1 and Th17 cells. Of note, Tc1 cells were also suboptimal in suppressing CD4-induced acute xenogeneic graft versus host disease (xGVHD) in vivo. Tc subtypes derived under various cytokine combinations revealed that IL-12-containing conditions resulted in less suppressive cells exhibiting dysregulated cytotoxic degranulation. RNA sequencing transcriptome analyses indicated differential regulation of inflammatory genes and...Continue Reading

References

May 1, 1991·The Journal of Experimental Medicine·P J PetersH J Geuze
Nov 1, 1988·Immunology Today·I R Cohen, H L Weiner
Jan 21, 1997·Proceedings of the National Academy of Sciences of the United States of America·K E BalashovH L Weiner
May 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·H JiangL Chess
May 17, 2001·Proceedings of the National Academy of Sciences of the United States of America·H JiangL Chess
Oct 3, 2001·The Journal of Experimental Medicine·J L McQualterC C Bernard
Oct 9, 2001·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·B G Winchester
Dec 10, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Javier ValenzuelaMatthew Mescher
Mar 27, 2003·Nature Reviews. Immunology·Matthias G von Herrath, Leonard C Harrison
Oct 29, 2003·Journal of Immunological Methods·Michael R BettsRichard A Koup
Nov 3, 2004·The Journal of Clinical Investigation·Stefanie SarantopoulosHarvey Cantor
Dec 18, 2004·Methods in Cell Biology·Michael R Betts, Richard A Koup
May 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Deepani K TennakoonNitin J Karandikar
Aug 7, 2007·Nature Immunology·Nicholas J WilsonRene de Waal Malefyt
Sep 10, 2008·The Journal of Experimental Medicine·Ivo SondereggerManfred Kopf
Sep 26, 2008·Blood·Katrina K HoyerAbul K Abbas
Nov 18, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hung-Rong YenCharles G Drake
Feb 23, 2010·Journal of Autoimmunity·Nathan R YorkNitin J Karandikar
Nov 26, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Agustina Tri EndhartiHaruhiko Suzuki
May 19, 2011·Nature Immunology·Mandy J McGeachy
Oct 24, 2012·Nature Reviews. Rheumatology·Richard M Pope, Shiva Shahrara
Dec 12, 2012·The Journal of Clinical Investigation·Magdalena HuberMichael Lohoff
Jun 5, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sterling B OrtegaNitin J Karandikar

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Datasets Mentioned

BETA
GM-CSF
GSE151204

Methods Mentioned

BETA
density gradient centrifugation
ELISA
Flow Cytometric
FACS
flow
RNAseq
flow cytometry

Software Mentioned

sleuth R package
IPA
sleuth
Ingenuity Pathway Analysis ( IPA )
R package
BD FACSDiva
kallisto
Graphpad Prism

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