B7/CD28 in central tolerance: costimulation promotes maturation of regulatory T cell precursors and prevents their clonal deletion.

Frontiers in Immunology
Maria HinterbergerLudger Klein

Abstract

According to the "two-step model," the intrathymic generation of CD4⁺ regulatory T (T(reg)) cells segregates into a first, T cell receptor (TCR)-driven phase and a second, cytokine-dependent phase. The initial TCR stimulus gives rise to a CD25⁺Foxp3⁻ developmental intermediate. These precursors subsequently require cytokine signaling to establish the mature CD25⁺Foxp3⁺ T(reg) cell phenotype. In addition, costimulation via CD28/B7 (CD80/86) axis is important for the generation of a T(reg) cell repertoire of normal size. Recent data suggest that CD28 or B7 deficient mice lack CD25⁺Foxp3⁻ T(reg) cell progenitors. However, these data leave open whether costimulation is also required at subsequent stages of T(reg) differentiation. Also, the fate of "presumptive" T(reg) cells carrying a permissive TCR specificity in the absence of costimulation remains to be established. Here, we have used a previously described TCR transgenic model of agonist-driven T(reg) differentiation in order to address these issues. Intrathymic adoptive transfer of T(reg) precursors indicated that costimulation is dispensable once the intermediate CD25⁺Foxp3⁻ stage has been reached. Furthermore, lack of costimulation led to the physical loss of presumptive T(r...Continue Reading

Citations

Mar 27, 2013·The Journal of Experimental Medicine·Jennifer E CowanGraham Anderson
Apr 20, 2012·Immunotherapy·Nina Pilat, Thomas Wekerle
Apr 15, 2014·Nature Immunology·Mathias Hauri-HohlSteven F Ziegler
Nov 1, 2015·Cellular and Molecular Life Sciences : CMLS·Charlotte SpitzNorbert Gerdes
Feb 13, 2014·Immunological Reviews·Alexandria HuynhLaurence A Turka
Aug 11, 2015·Frontiers in Immunology·Gabriel SkogbergOlov Ekwall
Mar 12, 2019·PLoS Biology·Marcin ŁyszkiewiczAndreas Krueger
Feb 11, 2012·Nature Reviews. Immunology·Chyi-Song HsiehChan-Wang J Lio
Mar 31, 2016·Nature Reviews. Immunology·Ming O Li, Alexander Y Rudensky
Apr 1, 2017·Cell Death and Differentiation·Daniel Y HuStephen R Daley
Jan 29, 2020·Annual Review of Immunology·Peter A SavageChristine H Miller
Oct 29, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daniel MarshallBenedict Seddon
Nov 14, 2018·Nature Reviews. Immunology·Ludger KleinChyi-Song Hsieh
May 4, 2017·Immunological Reviews·Stephen R DaleyDaniel H D Gray
Dec 14, 2011·Transplant International : Official Journal of the European Society for Organ Transplantation·Thomas Wekerle, Josep M Grinyó
Sep 19, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhanfeng LiangYong Zhao

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Methods Mentioned

BETA
transgenic
flow cytometry

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