CTLA-4 Engagement Inhibits Th2 but not Th1 Cell Polarisation

CTLA-4 deficient mice show severe lymphoproliferative disorders with T helper sub-population skewed toward the Th2 phenotype. In the present work, we investigated the role of CTLA-4 in T helper cell subset differentiation. Naïve CD4+ cells were stimulated with anti-CD3 and anti-CD28 mAbs in the pres...

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Main Authors: Vanessa Ubaldi, Lucia Gatta, Luigia Pace, Gino Doria, Claudio Pioli
Format: Article
Language:English
Published: Wiley 2003-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1080/10446670310001598519
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author Vanessa Ubaldi
Lucia Gatta
Luigia Pace
Gino Doria
Claudio Pioli
author_facet Vanessa Ubaldi
Lucia Gatta
Luigia Pace
Gino Doria
Claudio Pioli
author_sort Vanessa Ubaldi
collection DOAJ
description CTLA-4 deficient mice show severe lymphoproliferative disorders with T helper sub-population skewed toward the Th2 phenotype. In the present work, we investigated the role of CTLA-4 in T helper cell subset differentiation. Naïve CD4+ cells were stimulated with anti-CD3 and anti-CD28 mAbs in the presence of either IL-12 or IL-4 to induce polarisation to Th1 or Th2 cells, respectively. Under these two polarising conditions cells express comparable levels of CTLA-4. CTLA-4 was stimulated by plastic-bound mAb. The frequency of IFN-γ- and IL-4-producing cells were estimated by FACS analysis. In parallel cultures, polarised Th1 and Th2 cells were re-stimulated with anti-CD3 and anti-CD28 mAbs for 48 h and their culture supernatants analysed by ELISA. Results show that CTLA-4 engagement during differentiation inhibits polarisation of naïve CD4+ cells to the Th2 but not the Th1 cell subset. At variance, once cells are polarised, CTLA-4 engagement inhibits cytokine production in both effector Th2 and Th1 cells. Altogether these data indicate that CTLA-4 may interfere not only in the signalling involved in acute transcriptional activation of both Th1 and Th2 cells but also in the development of one of the Th cell subsets.
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spelling doaj-art-cd611b6e92fa470aa827610a8328bb092025-02-03T01:11:43ZengWileyClinical and Developmental Immunology1740-25221740-25302003-01-01101131710.1080/10446670310001598519CTLA-4 Engagement Inhibits Th2 but not Th1 Cell PolarisationVanessa Ubaldi0Lucia Gatta1Luigia Pace2Gino Doria3Claudio Pioli4Department of Biology, University of Tor Vergata, Rome I-00133, ItalySection of Toxicology and Biomedicine, ENEA C.R. Casaccia, Via Anguillarese 301, Rome I-00060, ItalyDepartment of Biology, University of Tor Vergata, Rome I-00133, ItalyDepartment of Biology, University of Tor Vergata, Rome I-00133, ItalySection of Toxicology and Biomedicine, ENEA C.R. Casaccia, Via Anguillarese 301, Rome I-00060, ItalyCTLA-4 deficient mice show severe lymphoproliferative disorders with T helper sub-population skewed toward the Th2 phenotype. In the present work, we investigated the role of CTLA-4 in T helper cell subset differentiation. Naïve CD4+ cells were stimulated with anti-CD3 and anti-CD28 mAbs in the presence of either IL-12 or IL-4 to induce polarisation to Th1 or Th2 cells, respectively. Under these two polarising conditions cells express comparable levels of CTLA-4. CTLA-4 was stimulated by plastic-bound mAb. The frequency of IFN-γ- and IL-4-producing cells were estimated by FACS analysis. In parallel cultures, polarised Th1 and Th2 cells were re-stimulated with anti-CD3 and anti-CD28 mAbs for 48 h and their culture supernatants analysed by ELISA. Results show that CTLA-4 engagement during differentiation inhibits polarisation of naïve CD4+ cells to the Th2 but not the Th1 cell subset. At variance, once cells are polarised, CTLA-4 engagement inhibits cytokine production in both effector Th2 and Th1 cells. Altogether these data indicate that CTLA-4 may interfere not only in the signalling involved in acute transcriptional activation of both Th1 and Th2 cells but also in the development of one of the Th cell subsets.http://dx.doi.org/10.1080/10446670310001598519
spellingShingle Vanessa Ubaldi
Lucia Gatta
Luigia Pace
Gino Doria
Claudio Pioli
CTLA-4 Engagement Inhibits Th2 but not Th1 Cell Polarisation
Clinical and Developmental Immunology
title CTLA-4 Engagement Inhibits Th2 but not Th1 Cell Polarisation
title_full CTLA-4 Engagement Inhibits Th2 but not Th1 Cell Polarisation
title_fullStr CTLA-4 Engagement Inhibits Th2 but not Th1 Cell Polarisation
title_full_unstemmed CTLA-4 Engagement Inhibits Th2 but not Th1 Cell Polarisation
title_short CTLA-4 Engagement Inhibits Th2 but not Th1 Cell Polarisation
title_sort ctla 4 engagement inhibits th2 but not th1 cell polarisation
url http://dx.doi.org/10.1080/10446670310001598519
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