Normal immune function of monocyte-derived dendritic cells from HIV-Infected individuals: Implications for immunotherapy

Dendritic cells (DC) are the most potent cells involved in the generation o f primary and secondary immune responses. To assess the feasibility of usin g autologous DC as immunotherapy for HIV disease, we analyzed a variety of immune parameters using DC isolated from HIV-infected (HIV+) individuals, a s well as DC obtained from HIV-uninfected (HIV-) individuals infected in vi tro with HIV, After stimulation with recombinant CD40 ligand (CD40LT), cyto kine and beta-chemokine production were similar by DC from HIV- donors infe cted in vitro with the CCR5-using HIV Ba-L strain (n = 8) compared with uni nfected DC from the same donors. Production of beta-chemokines, but not of cytokines, was increased by a CXCR4-using IIIB strain-infected DC (n = 7), Stimulation of HIV-infected DC with CD40LT decreased infection in Ba-L-infe cted DC, but had no effect on IIIB-infected DC. Consistent with this findin g, CD40LT down-regulated CCR5 and up-regulated CXCR4 expression on DC. Mono cyte-derived DC were also propagated from 15 HIV+ and 13 HIV- donors. They exhibited similar expression of costimulatory molecules and produced simila r amounts of IL-12, IL-10, and beta-chemokines, following stimulation. By c ontrast, stimulated PBMC from HIV+ patients exhibited decreased IL-12 and i ncreased IL-10 production. In summary, phenotype, cytokine secretion, and b eta-chemokine production by DC from HIV+ individuals were normal. These cel ls may prove useful in boosting cellular immune responses in HIV+ individua ls.