Implications of the accumulation of CXCR5+ NK cells in lymph nodes of HIV-1 infected patients
An-Liang Guo, Yan‐Mei Jiao, Qiwen Zhao, Hui-Huang Huang, Jianning Deng, Chao Zhang, Xing Fan, Ruonan Xu, Ji‐Yuan Zhang, Cheng Zhen, Zhiman Xie, Yingmei Qin, Jianqing Xu, Yu Yang, Ming Shi, Lei Huang, Jin‐Wen Song, Fu‐Sheng Wang
Abstract
BackgroundB cell follicles are immune-privileged sites where intensive HIV-1 replication and latency occur, preventing a permanent cure. Recent study showed that CXCR5+ NK cells in B cell follicles can inhibit SIV replication in African green monkeys, but this has not been reported in HIV-1 infected patients.MethodsLymphocytes and tissue sections of lymph node were collected from 11 HIV-1 positive antiretroviral therapy (ART)-naive and 19 HIV-1 negative donors. We performed immunofluorescence and RNA-scope to detect the location of CXCR5+ NK cells and its relationship with HIV-1 RNA, and performed flow cytometry and RNA-seq to analyze the frequency, phenotypic and functional characteristics of CXCR5+ NK cells. The CXCL13 expression were detected by immunohistochemistry.FindingsCXCR5+ NK cells, which accumulated in LNs from HIV-1 infected individuals, expressed high levels of activating receptors such as NKG2D and NKp44. CXCR5+ NK cells had upregulated expression of CD107a and β-chemokines, which were partially impaired in HIV-1 infection. Importantly, the frequency of CXCR5+NK cells was inversely related to the HIV-1 viral burden in LNs. In addition, CXCL13—the ligand of CXCR5—was upregulated in HIV-1 infected individuals and positively correlated with the frequency of CXCR5+ NK cells.InterpretationDuring chronic HIV-1 infection, CXCR5+ NK cells accumulated in lymph node, exhibit altered immune characteristics and underlying anti-HIV-1 effect, which may be an effective target for a functional cure of HIV-1.