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抗独特型抗体1F7可选择性抑制在HIV-1感染中被激活的细胞毒性T细胞。

The anti-idiotypic antibody 1F7 selectively inhibits cytotoxic T cells activated in HIV-1 infection.

作者信息

Grant M, Smaill F, Muller S, Kohler H, Rosenthal K

机构信息

Immune Network Research Ltd, Vancouver, Canada.

出版信息

Immunol Cell Biol. 2000 Feb;78(1):20-7. doi: 10.1046/j.1440-1711.2000.00879.x.

Abstract

Circulating CD8+ T lymphocyte numbers rise substantially following infection with HIV-1. This expanded CD8+ T cell population includes HIV-specific CTL and CTL that kill activated uninfected CD4+ lymphocytes. Experimental, epidemiological and clinical evidence supports the possibility that expansion of CD8+ CTL contributes to CD4+ T cell depletion and disease progression in human HIV infection. Therefore, modulation of CD8+ T cell numbers or of certain CD8+ CTL activated in HIV-infected individuals may be beneficial. It was found that 1F7, a mAb against an idiotype common to anti-HIV and anti-simian immunodeficiency virus (SIV) antibodies, selectively inhibited both anti-HIV CTL and CTL against uninfected CD4+ T cells. Alloantigen-specific CTL and NK cells from either HIV-infected individuals or controls were unaffected by 1F7. Prolonged incubation of CD8+ T cells from HIV-infected individuals with 1F7 induces apoptosis, which was shown to be reflected functionally in reduced total CTL activity and in especially reduced CTL activity against uninfected CD4+ lymphocytes. The selective reactivity of 1F7 with certain CD8+ CTL could be applied towards the modulation of CD8+ T cell responses involved in AIDS pathogenesis.

摘要

感染HIV-1后,循环CD8+ T淋巴细胞数量大幅上升。这种扩增的CD8+ T细胞群体包括HIV特异性CTL以及可杀伤活化的未感染CD4+淋巴细胞的CTL。实验、流行病学及临床证据均支持这样一种可能性,即CD8+ CTL的扩增会导致人类HIV感染中CD4+ T细胞耗竭及疾病进展。因此,调节HIV感染个体中CD8+ T细胞数量或某些活化的CD8+ CTL可能有益。研究发现,1F7(一种针对抗HIV和抗猴免疫缺陷病毒(SIV)抗体共有的独特型的单克隆抗体)可选择性抑制抗HIV CTL以及针对未感染CD4+ T细胞的CTL。来自HIV感染个体或对照的同种异体抗原特异性CTL和NK细胞不受1F7影响。将HIV感染个体的CD8+ T细胞与1F7长时间孵育可诱导细胞凋亡,这在功能上表现为总CTL活性降低,尤其是针对未感染CD4+淋巴细胞的CTL活性降低。1F7与某些CD8+ CTL的选择性反应性可用于调节参与艾滋病发病机制的CD8+ T细胞反应。

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