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International Immunology Advance Access originally published online on July 22, 2009
International Immunology 2009 21(9):1025-1036; doi:10.1093/intimm/dxp068
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Modulation of the TCR stimulation strength can render human activated CD4+ T cells suppressive

Grégory Noël1,*, Carine Brinster1,2,4,*, Gilbert Semana3,2 and Denis Bruniquel1,2

1 UPRES 3889, Faculté de Médecine, Laboratoire d'Immuno-Hématologie, 2 avenue du Professeur Léon Bernard, 35043 Rennes cedex, France
2 Etablissement Français du Sang-Bretagne, rue Pierre-Jean Gineste, BP 91614, 35016 Rennes cedex, France
3 INSERM Unité 917, Faculté de Médecine, 2 avenue du Professeur Léon Bernard, 35043 Rennes cedex, France
4 Present address: Institut pour la Recherche sur le Cancer de Lille, Centre de Recherche Jean-Pierre Aubert, INSERM Unité 837, 1, place de verdun, 59045 Lille cedex, France

Correspondence to: D. Bruniquel; E-mail address: denis.bruniquel{at}univ-rennes1.fr

In this study, we explored the potential of human naive CD4+ T cells to acquire regulatory properties upon stimulation. We demonstrated that, in vitro, pre-activated naive CD4+CD25–CD45RA+ T cells could become anergic and suppressive CD4+CD25+ T cells upon lower intensity TCR stimulation. These CD4+CD25+ T cells generated in vitro potently suppress the proliferation of allogenic CD4+CD25– T cells independently of cytokines and in a contact-dependent manner. Our data indicate that expression of Foxp3 is not necessary to induce the suppressive T cell activity. We demonstrate that these CD4+CD25+ T cells are unresponsive upon re-stimulation and that their suppressive activity is transient. However, we showed that the anergy and the suppressive function could be reversed by increasing the stimulus and their level of activation. We concluded from our data that these anergy and suppressive activities are related to a fine tuning of TCR activation threshold.

Keywords: cell activation, T cells, tolerance/suppression/anergy

* These authors contributed equally to this work.

Transmitting editor: R. A. Flavell

Received 22 September 2008, accepted 23 June 2009.


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