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*
Experimental Immunology Branch and
Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
Department of Immunology/Microbiology and Medicine, Rush-Presbyterian-St. Lukes 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
-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
-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
-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
-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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