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The Journal of Immunology, 1999, 163: 1666-1673.
Copyright © 1999 by The American Association of Immunologists

Normal Immune Function of Monocyte-Derived Dendritic Cells from HIV-Infected Individuals: Implications for Immunotherapy

Claire Chougnet*, Sandra S. Cohen{dagger}, Tatsuyoshi Kawamura{dagger}, Alan L. Landay{ddagger}, Harold A. Kessler{ddagger}, Elaine Thomas§, Andrew Blauvelt{dagger} and Gene M. Shearer1,*

* Experimental Immunology Branch and {dagger} Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; {ddagger} Department of Immunology/Microbiology and Medicine, Rush-Presbyterian-St. Luke’s Medical Center, Chicago, IL 60617; and § Immunex Corp., Seattle, WA 98101

Dendritic cells (DC) are the most potent cells involved in the generation of primary and secondary immune responses. To assess the feasibility of using autologous DC as immunotherapy for HIV disease, we analyzed a variety of immune parameters using DC isolated from HIV-infected (HIV+) individuals, as well as DC obtained from HIV-uninfected (HIV-) individuals infected in vitro with HIV. After stimulation with recombinant CD40 ligand (CD40LT), cytokine and {beta}-chemokine production were similar by DC from HIV- donors infected in vitro with the CCR5-using HIV Ba-L strain (n = 8) compared with uninfected 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-infected DC, but had no effect on IIIB-infected DC. Consistent with this finding, CD40LT down-regulated CCR5 and up-regulated CXCR4 expression on DC. Monocyte-derived DC were also propagated from 15 HIV+ and 13 HIV- donors. They exhibited similar expression of costimulatory molecules and produced similar amounts of IL-12, IL-10, and {beta}-chemokines, following stimulation. By contrast, stimulated PBMC from HIV+ patients exhibited decreased IL-12 and increased IL-10 production. In summary, phenotype, cytokine secretion, and {beta}-chemokine production by DC from HIV+ individuals were normal. These cells may prove useful in boosting cellular immune responses in HIV+ individuals.







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