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CUTTING EDGE |
*
Dermatology Branch, National Cancer Institute, and Divisions of
Viral Products and
Cell and Gene Therapy, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892
HIV-infected dendritic cells (DC) efficiently transmit infection
to CD4+ T cells during the process of T cell activation. To
further understand interactions between DC and HIV, cytokine regulation
of HIV coreceptors on cultured Langerhans cells (cLC, as prototypes of
mature DC) was studied. Expression of cell surface CXCR4 on cLC was
up-regulated by IL-4 and TGF-ß1 and inhibited by IFN-
, IFN-ß,
and IFN-
, whereas cytokines did not appreciably regulate CCR5.
Changes in cell surface CXCR4 expression on cLC correlated with T
cell-tropic (X4)-HIV envelope-mediated syncytium formation and X4-HIV
infection levels. A relative increase in the ratio of type 2/type 1
cytokine production, which can occur in HIV disease, may up-regulate
CXCR4 expression on mature DC and promote infection by X4 viruses.
Importantly, these findings suggest that cytokine dysregulation may be
linked to the emergence of X4-HIV strains as HIV-infected individuals
progress to AIDS.
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