CULTURED BLOOD DENDRITIC CELLS RETAIN HIV-1 ANTIGEN-PRESENTING CAPACITY FOR MEMORY CTL DURING PROGRESSIVE HIV-1 INFECTION

Dendritic cells (DC) are potent APC that may be involved in the pathog enesis of HIV-1 infection. We studied the APC function of DC from HIV- 1-infected subjects that were derived from monocyte-depleted PBMC by c ulture in human IL-4 and human granulocyte-macrophage CSF. The culture d cells from the HIV-1-infected subjects had similar morphology and ph enotype of mature DC (CD80 = 41 +/- 8%, CD86 = 77 +/- 5%, CD40 = 87 +/ - 6%, CD1a = 1 +/- 1%) to DC cultured from seronegative subjects. The yield of these DC was lower than from HIV-1-seronegative subjects (4 /- 0% vs 11 +/- 2%, p < 0.01), and the lower DC yields correlated with lower numbers of blood CD4(+) T cells (r = 0.60, p < 0.01) and higher plasma viral load (r = -0.49, p < 0.01). DC from HIV-1-infected subje cts were infected with recombinant vaccinia virus vectors expressing G ag, Pol, and Env and were able to stimulate equal or higher levels of MHC class I-restricted, anti-HIV-1 memory CTL (CTLm) than were similar ly treated, autologous B lymphocyte cell lines. DC pulsed with peptide s representing HIV-1 CTL epitopes stimulated higher levels of anti-HIV -1 CTLm responses than did DC infected with the vaccinia virus-HIV-1 c onstructs, Allogeneic, MHC class I-matched DC also stimulated anti-HIV -1 CTLm activity in cells from HIV-1-infected subjects. DC from early and late stages of HIV-1 infection had a similar ability to activate C TLm specific for targets expressing either HIV-1 genes via vaccinia vi rus vectors or HIV-1 immunodominant synthetic peptides. However, DC fr om either early or late stages of HIV-1 infection could not overcome t he defect in anti-HIV-1 CTLm response in advanced infection.