Nature Immunology：HIV吓晕免疫细胞
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
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