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标题：In vivo expansion of naive and activated CD4+CD25+FOXP3+ regulatory T cell populations in interleukin-2–treated HIV patients
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作者：Laurence Weiss ; Fabrice A. Letimier ; Matthieu Carriere 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：23
页码：10632-10637
DOI：10.1073/pnas.1000027107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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+CD25loCD127loFOXP3+ and CD4+CD25hiCD127loFOXP3hi) 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+CD25hiFOXP3+ 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.
关键词：molecular profiling ; immune-based therapy