Implications of the accumulation of CXCR5(+) NK cells in lymph nodes of HIV-1 infected patients

BACKGROUND: B 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. METHODS: Lymphocytes 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. FINDINGS: CXCR5(+) 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. INTERPRETATION: During 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.