Antigen-presenting cell modulation induces a memory response to p24 in peripheral blood leukocytes from human...

The accurate determination of human immunodeficiency virus type 1 (HIV-1)-specific proliferative responses is critically important when evaluating immune recovery after highly active antiretroviral therapy. Using a new assay to enhance proliferative responses to recall and HIV antigen, we addressed the questions of whether viral load affects cellular immunity and whether long-term viral load suppression results in loss of antigen-specific responder cells. This assay is based on the fact that lipopolysaccharide (LPS) can augment proliferative responses to antigen after monocyte adherence to a tissue culture plate. Twenty-six HIV-1-infected individuals donated peripheral blood leukocytes (PBL). Proliferation assays against p24, using LPS and cell adherence, were performed on all samples. Medical record abstraction provided information on CD4 cell nadir and time of viral load suppression. PBL from HIV-1-infected individuals with a viral load of <200 copies/ml had a significant proliferative response and a stimulation index of >5 to p24 (12 of 15) compared to those with a viral burden (2 of 11), using the LPS-adherence assay. Proliferative responses to p24 could be found in PBL from virally suppressed donors independent of the CD4 cell nadirs and in the majority of the donors who were virally suppressed for >10 months (7 of 10). The data presented here demonstrate that LPS and monocyte adherence provide a sensitive and specific way to boost proliferative responses to recall and HIV antigens.