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* HIV Immunopathogenesis Laboratory, Wistar Institute, and
Children’s Hospital of Philadelphia, Division of Immunologic and Infectious Diseases, Philadelphia, PA 19104;
Philadelphia Field Initiation Group for HIV Trials, Philadelphia, PA 19103; and
Laboratory for Immunological Research, Schering-Plough, Dardilly, France
Dendritic cells (DC) have an instrumental role in the activation
and function of both innate and adaptive immune responses. In humans,
at least two distinct DC subsets have been characterized based on
phenotypic markers: the myeloid DC (MDC) and the plasmacytoid DC (PDC).
Both subsets are critical producers of cytokines (IL-12 for MDC and
type I/II IFNs for PDC) and are functionally different. We show in this
study that HIV+ individuals have a significant decrease in
the number of the
Lin-HLA-DR+CD123+ and
BDCA-2+ PDC compared with uninfected donors
(p = 0.0001). HIV+ individuals also
have a sustained impairment in viral-induced IFN-
production
(p < 0.0001). The decrease of the PDC subsets did
not correlate with CD4 count or viral load and was not reversed in
subjects under virally suppressive treatment, suggesting an
irreversible change after infection. By contrast, the absolute number
and median frequency of MDC in HIV-infected individuals were similar to
those observed in uninfected controls, while a significant decrease was
present in subjects with >5000 HIV-1 copies/ml. The inverse
association with viral load of the MDC number, but not of IFN-
secretion or the number of PDC, suggests a role for MDC in viral
control. Our data suggest that DC subsets are differentially
reconstituted during the immune recovery associated with antiviral
therapy. The persistent impairment of certain DC subsets may result in
a sustained defect in DC-mediated innate immune functions despite an
effective treatment regimen.
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G. M. Bahr Non-specific immunotherapy of HIV-1 infection: potential use of the synthetic immunodulator murabutide J. Antimicrob. Chemother., January 1, 2003; 51(1): 5 - 8. [Full Text] [PDF]
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M. Wysocka, M. H. Zaki, L. E. French, J. Chehimi, M. Shapiro, S. E. Everetts, K. S. McGinnis, L. Montaner, and A. H. Rook Sezary syndrome patients demonstrate a defect in dendritic cell populations: effects of CD40 ligand and treatment with GM-CSF on dendritic cell numbers and the production of cytokines Blood, October 16, 2002; 100(9): 3287 - 3294. [Abstract] [Full Text] [PDF]
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