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

Autor: Matthieu Carrière, Brice Targat, Arndt Benecke, Lars Rogge, Laurence Weiss, Sylvie Maiella, Vladimira Donkova-Petrini, Yves Levy, Fabrice A. Letimier
Přispěvatelé: Service d'immunologie [HEGP, Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Régulation des Infections Rétrovirales, Institut Pasteur [Paris], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Immunorégulation, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut des Hautes Etudes Scientifiques (IHES), IHES, Service d'immunologie clinique [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), F.A.L. and S.M. were supported by predoctoral fellowships from the ANRS and the Ligue Nationale Contre le Cancer, respectively. M.C. has received a post-doctoral fellowship from the ANRS. V.D.P. was supported by Sidaction. Work in L.W.'s laboratory was supported by funds from ANRS and Sidaction. Work in L.R.'s laboratory was supported by funds from Sidaction, the European Community (LSHG-CT-2005-005203 'MUGEN'), and institutional funds from Institut Pasteur (GPH n°2), Guellaen, Georges, Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut des Hautes Études Scientifiques (IHES)
Rok vydání: 2010
Předmět:
Zdroj: Proceedings of the National Academy of Sciences of the United States of America
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⟩
Proceedings of the National Academy of Sciences of the United States of America, 2010, 107 (23), pp.10632-7. ⟨10.1073/pnas.1000027107⟩
ISSN: 1091-6490
0027-8424
DOI: 10.1073/pnas.1000027107
Popis: 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.
Databáze: OpenAIRE
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