DENDRITIC CELLS PERSISTENTLY STIMULATE ANTIBODY-RESPONSES TO HIV IN SEROPOSITIVE INDIVIDUALS

Objectives: B-cell hyperactivity and hypergammaglobulinaemia with high levels of HIV-1-specific antibody occur during HIV-1 infection. We in vestigated the role played by antigen-presenting cells (APC) in the on going production of antibody. Methods: Adherent monocytes and non-adhe rent low density dendritic cells were enriched from peripheral blood o f patients at different stages of HIV-1 infection (Centers for Disease Control and Prevention categories II, III and IV) and from control su bjects at high or low risk of HIV infection. Different concentrations of lymphocytes were cultured in 20 ml hanging drops in the presence or absence of autologous dendritic cells or monocytes. Antibodies to p24 and gp120 were assessed by enzyme-linked immunosorbent assay. Results : Lymphocytes taken from asymptomatic HIV-1-seropositive subjects and depleted of APC produced low or moderate levels of antibody to gp120 o r p24 in vitro. However, adding back autologous dendritic cells signif icantly enhanced antibody production, although fewer samples showed re sponses to p24 than to gp120. Less antibody production was stimulated using cells from patients with persistent generalized lymphadenopathy, or if monocytes rather than dendritic cells were added back. Little o r no antibody was produced by cells from patients with AIDS and no ant ibody was detected in cultures of cells from seronegative individuals with low or high risk for infection. Conclusions: The evidence suggest s that ongoing humoral responses to HIV-1 are fuelled by dendritic cel ls. Thus, the dominance of humoral over cell-mediated responses in HIV -1 infection may depend upon signalling via dendritic cells. Changes i n signalling by dendritic cells could be central to the immunologic fe atures of HIV-1 infection.