CD4+CD19+ conjugates favor HIV-1 infection and latency during chronic HIV-1 infection.

OBJECTIVE: CD4CD19 conjugates play an important role in regulating antibody responses and follicular helper T cells development in animal models. However, little is known regarding the characteristic of CD4CD19 conjugates in humans with chronic HIV-1 infection.

METHODS: The numbers of CD4CD19 conjugates were counted in 86 HIV-1-infected patients, including 66 typical progressors (TPs) and 20 complete responders (CRs). CD4CD19 conjugates were sorted by flow cytometry and dissociated into CD4 T singlets and CD19 B singlets. The phenotypes of these cells were analyzed in both TPs and CRs, and the levels of HIV-1 DNA in CD4CD19 conjugates were measured in 10 CRs.

RESULTS: We identified CD4CD19 cells were one type of T-B conjugates in peripheral blood, and the numbers and percentages of CD4CD19 conjugates decreased with HIV-1 disease progression. Phenotypic analysis showed CD4CD19 conjugates expressed higher levels of surface CD32. mRNA analysis found that the mRNA levels for CD32b were significantly higher compared with CD32a in CD4CD19 conjugates. Further analysis found CD4CD19 conjugates expressed high levels of CCR7 and CXCR5 than CD4 T and CD19 B singlets. Virus infectivity assay showed CD4CD19 conjugates expressed higher levels of HIV-1-p24 than CD4CD19 cells. CD4CD19 conjugates in lymph node from TPs expressed higher levels of HIV-1-p24 than CD4CD19 conjugates in respective peripheral blood. Importantly, CD4CD19 conjugates from CRs contained higher levels of HIV-1 DNA than total CD4 T cells.

CONCLUSION: Our study indicates that CD4CD19 conjugates actively participate in HIV-1 infection and latency, and may serve as a new cellular target to eliminate latency.