在HIV感染者体内的一种关键免疫细胞中，免疫系统中一种已知抑制因子的数量大大增加了，这一最新的研究成果发表在11月号的《自然—免疫学》期刊上。
Bruce Walker和同事对HIV呈阳性并且快速发展出疾病的人进行了研究，他们发现，与那些感染HIV但长期无疾病进展的人相比，这些人的CD4+T淋巴结中CTLA-4 的表达水平有明显增加。与此同时，他们对接受高活性抗逆转录病毒治疗的患者在治疗前后CD4+T细胞上CTLA-4的表达进行了对比，发现在治疗前，患者体内有更高水平的与T细胞相关的CD4+T。他们还发现，阻断 CTLA-4 的活性能够提高免疫功能。
新研究表明，降低CD4+T细胞中CTLA-4的表达也许能提供一种新方法，提高HIV感染者的淋巴细胞功能。（科学时报）
原始出处:
Nature Immunology 8, 1246 - 1254 (2007)
Published online: 30 September 2007 | doi:10.1038/ni1515
Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction
Daniel E Kaufmann1,7, Daniel G Kavanagh1,7, Florencia Pereyra1,2, John J Zaunders3, Elizabeth W Mackey1, Toshiyuki Miura1,4, Sarah Palmer5, Mark Brockman1,4, Almas Rathod1, Alicja Piechocka-Trocha1,4, Brett Baker1, Baogong Zhu6, Sylvie Le Gall1, Michael T Waring1,4, Ryan Ahern1, Kristin Moss1, Anthony D Kelleher3, John M Coffin5, Gordon J Freeman6, Eric S Rosenberg1 & Bruce D Walker1,4
In progressive viral infection, antiviral T cell function is impaired by poorly understood mechanisms. Here we report that the inhibitory immunoregulatory receptor CTLA-4 was selectively upregulated in human immunodeficiency virus (HIV)–specific CD4+ T cells but not CD8+ T cells in all categories of HIV-infected subjects evaluated, with the exception of rare people able to control viremia in the absence of antiretroviral therapy. CTLA-4 expression correlated positively with disease progression and negatively with the capacity of CD4+ T cells to produce interleukin 2 in response to viral antigen. Most HIV-specific CD4+ T cells coexpressed CTLA-4 and another inhibitory immunoregulatory receptor, PD-1. In vitro blockade of CTLA-4 augmented HIV-specific CD4+ T cell function. These data, indicating a reversible immunoregulatory pathway selectively associated with CD4+ T cell dysfunction, provide a potential target for immunotherapy in HIV-infected patients.
Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115, USA.
Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Centre for Immunology, St Vincent's Hospital, Darlinghurst, New South Wales 2010, Australia.
Howard Hughes Medical Institute, Chevy Chase, Maryland 20185, USA.
HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
These authors contributed equally to this work.
Correspondence to: Daniel E Kaufmann1,7 e-mail: dkaufmann@partners.org
