Peripheral Vγ9Vδ2 T Cells Are a Novel Reservoir of Latent HIV Infection

Eradication of HIV infection will require the identification of all cellular reservoirs that harbor latent infection. Despite low or lack of CD4 receptor expression on Vδ2 T cells, infection of these cells has previously been reported. We found that upregulation of the CD4 receptor may render primary Vδ2 cells target for HIV infection in vitro and we propose that HIV-induced immune activation may allow infection of γδ T cells in vivo. We assessed the presence of latent HIV infection by measurements of DNA and outgrowth assays within Vδ2 cells in 18 aviremic patients on long-standing antiretroviral therapy. In 14 patients we recovered latent but replication-competent HIV from highly purified Vδ2 cells demonstrating that peripheral Vδ2 T cells are a previously unrecognized reservoir in which latent HIV infection is unexpectedly frequent.

根除人类免疫缺陷病毒（HIV, Human Immunodeficiency Virus）感染，需精准识别所有携带潜伏感染的细胞病毒储存库。尽管Vδ2 T细胞（Vδ2 T cell）表面CD4受体（CD4 receptor）的表达水平较低或缺失，但此前已有研究证实此类细胞可被HIV感染。本研究发现，CD4受体的上调可使原代Vδ2细胞在体外成为HIV感染的靶细胞，并据此提出：HIV诱导的免疫激活可能促使体内γδ T细胞（γδ T cell）发生感染。我们对18名接受长期抗逆转录病毒治疗（antiretroviral therapy, ART）的病毒学抑制（aviremic）患者的Vδ2细胞，通过DNA检测与复苏培养试验（outgrowth assay）评估其中潜伏HIV感染的存在情况。在14名患者中，我们从高纯度Vδ2细胞中分离得到了潜伏但具备复制能力的HIV，这表明外周血Vδ2 T细胞是一类此前未被认知的病毒储存库，其中潜伏HIV感染的发生率出人意料地高。