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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3249-3256. Prepublished online as a Blood First Edition Paper on July 22, 2004; DOI 10.1182/blood-2004-01-0365. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-01-0365v1 104/10/3249    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Weiss, L. Articles by Levy, Y. Search for Related Content PubMed PubMed Citation Articles by Weiss, L. Articles by Levy, Y. Related Collections Gene Expression Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Human immunodeficiency virus–driven expansion of CD4+CD25+ regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients Laurence Weiss, Vladimira Donkova-Petrini, Laure Caccavelli, Michèle Balbo, Cédric Carbonneil, and Yves Levy From the Institut National de la Santé et de la Recherche Médicale (INSERM) U430 and University Paris V, Paris, France; Department of Immunology, Hôpital Européen Georges Pompidou, Paris, France; INSERM U421, Paris and University Paris XII, Créteil, France; and Service of Clinical Immunology, Hôpital Henri Mondor, Créteil, France. The present study demonstrates that CD4+CD25+ T cells, expanded in peripheral blood of HIV-infected patients receiving highly active antiretroviral therapy (HAART), exhibit phenotypic, molecular, and functional characteristics of regulatory T cells. The majority of peripheral CD4+CD25+ T cells from HIV-infected patients expressed a memory phenotype. They were found to constitutively express transcription factor forkhead box P3 (Foxp3) messengers. CD4+CD25+ T cells weakly proliferated to immobilized anti-CD3 monoclonal antibody (mAb) and addition of soluble anti-CD28 mAb significantly increased proliferation. In contrast to CD4+CD25– T cells, CD4+CD25+ T cells from HIV-infected patients did not proliferate in response to recall antigens and to p24 protein. The proliferative capacity of CD4 T cells to tuberculin, cytomegalovirus (CMV), and p24 significantly increased following depletion of CD4+CD25+ T cells. Furthermore, addition of increasing numbers of CD4+CD25+ T cells resulted in a dose-dependent inhibition of CD4+CD25– T-cell proliferation to tuberculin and p24. CD4+CD25+ T cells responded specifically to p24 antigen stimulation by expressing transforming growth factor (TGF-) and interleukin 10 (IL-10), thus indicating the presence of p24-specific CD4+ T cells among the CD4+CD25+ T-cell subset. Suppressive activity was not dependent on the secretion of TGF- or IL-10. Taken together, our results suggest that persistence of HIV antigens might trigger the expansion of CD4+CD25+ regulatory T cells, which might induce a tolerance to HIV in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Cabrera, D. Burzyn, J. Mundinano, M. C. Courreges, G. Camicia, D. Lorenzo, H. Costa, S. R. Ross, I. Nepomnaschy, and I. 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Zaunders, S. Ip, M. L. Munier, D. E. Kaufmann, K. Suzuki, C. Brereton, S. C. Sasson, N. Seddiki, K. Koelsch, A. Landay, et al. Infection of CD127+ (Interleukin-7 Receptor+) CD4+ Cells and Overexpression of CTLA-4 Are Linked to Loss of Antigen-Specific CD4 T Cells during Primary Human Immunodeficiency Virus Type 1 Infection. J. Virol., October 1, 2006; 80(20): 10162 - 10172. [Abstract] [Full Text] [PDF] C. Bourgeois and B. Stockinger CD25+CD4+ Regulatory T Cells and Memory T Cells Prevent Lymphopenia-Induced Proliferation of Naive T Cells in Transient States of Lymphopenia J. Immunol., October 1, 2006; 177(7): 4558 - 4566. [Abstract] [Full Text] [PDF] G. A. Diaz and D. M. Koelle Human CD4+ CD25high Cells Suppress Proliferative Memory Lymphocyte Responses to Herpes Simplex Virus Type 2. J. Virol., August 1, 2006; 80(16): 8271 - 8273. [Abstract] [Full Text] [PDF] D. Xu, J. Fu, L. Jin, H. Zhang, C. Zhou, Z. Zou, J.-M. Zhao, B. Zhang, M. Shi, X. Ding, et al. 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