在HIV感染者體內(nèi)的一種關(guān)鍵免疫細(xì)胞中,，免疫系統(tǒng)中一種已知抑制因子的數(shù)量大大增加了，這一最新的研究成果發(fā)表在11月號(hào)的《自然—免疫學(xué)》期刊上。
Bruce Walker和同事對(duì)HIV呈陽(yáng)性并且快速發(fā)展出疾病的人進(jìn)行了研究，他們發(fā)現(xiàn)，與那些感染HIV但長(zhǎng)期無(wú)疾病進(jìn)展的人相比,，這些人的CD4+T淋巴結(jié)中CTLA-4 的表達(dá)水平有明顯增加。與此同時(shí),，他們對(duì)接受高活性抗逆轉(zhuǎn)錄病毒治療的患者在治療前后CD4+T細(xì)胞上CTLA-4的表達(dá)進(jìn)行了對(duì)比,，發(fā)現(xiàn)在治療前，患者體內(nèi)有更高水平的與T細(xì)胞相關(guān)的CD4+T,。他們還發(fā)現(xiàn),，阻斷 CTLA-4 的活性能夠提高免疫功能。
新研究表明,，降低CD4+T細(xì)胞中CTLA-4的表達(dá)也許能提供一種新方法,，提高HIV感染者的淋巴細(xì)胞功能。（科學(xué)時(shí)報(bào)）
原始出處:
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: [email protected]
