Broadly-specific Cytotoxic T Cells Targeting Multiple HIV Antigens Are Expanded From HIV plus Patients: Implications for Immunotherapy
Broadly-specific Cytotoxic T Cells Targeting Multiple HIV Antigens Are Expanded From HIV plus Patients: Implications for Immunotherapy
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DOI：
10.1038/mt.2014.207
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发表时间：
2015-02-01
影响因子：
12.4
通讯作者：
Bollard, Catherine
中科院分区：
文献类型：
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作者：
Lam, Sharon;Sung, Julia;Bollard, Catherine
抗逆转录病毒疗法（ART）不能根除人类免疫缺陷病毒1型（HIV-1）感染。因此，迫切需要开发新的治疗方法来增强这种疾病的抗hiv免疫。T细胞疗法在这方面很有吸引力，因为T细胞具有增殖、迁移的能力，而且它们的抗原特异性降低了脱靶效应的可能性。然而，过去在HIV-1感染的人类研究中，给予具有有限特异性的T细胞未能提供不依赖art的长期病毒控制。在这项研究中，我们试图从接受抑制性抗逆转录病毒治疗的HIV感染患者身上扩展功能性、广泛特异性的细胞毒性T细胞（hxtc），作为开发用于未来HIV根除方案的细胞疗法的第一步。7例接受抑制性抗逆转录病毒治疗的HIV阳性患者的血液样本用于获得hxtc。多抗原特异性是通过T细胞与抗原呈递细胞共培养实现的，这些细胞含有代表Gag、Pol和Nef的肽。除了两种细胞系外，其他细胞系对这三种抗原都具有多特异性。hxtc通过释放促炎细胞因子、特异性裂解抗原脉冲靶点以及在体外抑制HIV复制的能力证明了其有效性。总之，我们能够产生广泛特异性的细胞毒性T细胞系，同时靶向多种HIV抗原，并显示出强大的抗病毒功能。
Antiretroviral therapy (ART) is unable to eradicate human immunodeficiency virus type 1 (HIV-1) infection. Therefore, there is an urgent need to develop novel therapies for this disease to augment anti-HIV immunity. T cell therapy is appealing in this regard as T cells have the ability to proliferate, migrate, and their antigen specificity reduces the possibility of off-target effects. However, past human studies in HIV-1 infection that administered T cells with limited specificity failed to provide ART-independent, long-term viral control. In this study, we sought to expand functional, broadly-specific cytotoxic T cells (HXTCs) from HIV-infected patients on suppressive ART as a first step toward developing cellular therapies for implementation in future HIV eradication protocols. Blood samples from seven HIV+ patients on suppressive ART were used to derive HXTCs. Multiantigen specificity was achieved by coculturing T cells with antigen-presenting cells pulsed with peptides representing Gag, Pol, and Nef. All but two lines were multispecific for all three antigens. HXTCs demonstrated efficacy as shown by release of proinflammatory cytokines, specific lysis of antigen-pulsed targets, and the ability to suppress HIV replication in vitro. In conclusion, we are able to generate broadly-specific cytotoxic T cell lines that simultaneously target multiple HIV antigens and show robust antiviral function.