In vivo expansion of naive and activated CD4+CD25+FOXP3+ regulatory T cell populations in interleukin-2-treated HIV patients.

Abstract : HIV-1 infection is characterized by a progressive decline in CD4(+) T cells leading to a state of profound immunodeficiency. IL-2 therapy has been shown to improve CD4(+) counts beyond that observed with antiretroviral therapy. Recent phase III trials revealed that despite a sustained increase in CD4(+) counts, IL-2-treated patients did not experience a better clinical outcome [Abrams D, et al. (2009) N Engl J Med 361(16):1548-1559]. To explain these disappointing results, we have studied phenotypic, functional, and molecular characteristics of CD4(+) T cell populations in IL-2-treated patients. We found that the principal effect of long-term IL-2 therapy was the expansion of two distinct CD4(+)CD25(+) T cell populations (CD4(+)CD25(lo)CD127(lo)FOXP3(+) and CD4(+)CD25(hi)CD127(lo)FOXP3(hi)) that shared phenotypic markers of Treg but could be distinguished by the levels of CD25 and FOXP3 expression. IL-2-expanded CD4(+)CD25(+) T cells suppressed proliferation of effector cells in vitro and had gene expression profiles similar to those of natural regulatory CD4(+)CD25(hi)FOXP3(+) T cells (Treg) from healthy donors, an immunosuppressive T cell subset critically important for the maintenance of self-tolerance. We propose that the sustained increase of the peripheral Treg pool in IL-2-treated HIV patients may account for the unexpected clinical observation that patients with the greatest expansion of CD4(+) T cells had a higher relative risk of clinical progression to AIDS.
Type de document :
Article dans une revue
Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2010, 107 (23), pp.10632-7. 〈10.1073/pnas.1000027107〉
Liste complète des métadonnées

Littérature citée [37 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00489719
Contributeur : Georges Guellaen <>
Soumis le : lundi 7 juin 2010 - 08:06:23
Dernière modification le : jeudi 11 janvier 2018 - 06:21:31
Document(s) archivé(s) le : vendredi 17 septembre 2010 - 12:39:48

Fichier

195704_1_merged_1271953701.pdf
Fichiers produits par l'(les) auteur(s)

Identifiants

Citation

Laurence Weiss, Fabrice Letimier, Matthieu Carriere, Sylvie Maiella, Vladimira Donkova-Petrini, et al.. In vivo expansion of naive and activated CD4+CD25+FOXP3+ regulatory T cell populations in interleukin-2-treated HIV patients.. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2010, 107 (23), pp.10632-7. 〈10.1073/pnas.1000027107〉. 〈inserm-00489719〉

Partager

Métriques

Consultations de la notice

369

Téléchargements de fichiers

255