AIDSWEEKLY Plus; Monday, August 22, 2005
Staff Medical Writers

"Current immunological opinion holds that myeloid dendritic cell (mDC) precursors migrate from the blood to the tissues, where they differentiate into immature dermal-and Langerhans-type dendritic cells (DC).

"Tissue DC require appropriate signals from pathogens or inflammatory cytokines to mature and migrate to secondary lymphoid tissue," scientists in England report.

"We show that purified blood mDC cultured in vitro with GM-CSF and IL-4, but in the absence of added exogenous maturation stimuli, rapidly differentiate into two maturational and phenotypically distinct populations.

"The major population resembles immature dermal DC, being positive for CD11b, CD1a, and DC-specific ICAM-3-grabbing nonintegrin. They express moderate levels of MHC class II and low levels of costimulatory molecules," wrote S. Patterson and colleagues at Chelsea & Westminster Hospital in London.

"The second population is CD11b-/low and lacks CD1a and DC-specific ICAM-3-grabbing nonintegrin but expresses high levels of MHC class 11 and costimulatory molecules. Expression of CCR7 on the CD11b-/low population and absence on the CD11b+ cells further supports the view that these cells are mature and immature, respectively," investigators said.

The authors continued, "Differentiation into mature and immature populations was not blocked by polymyxin B, an inhibitor of LPS. Neither population labeled for Langerin, E-cadherin, or CCR6 molecules expressed by Langerhans cells.

"Stimulation of 48-hour cultured DC with LPS, CD40L, or poly(I-C) caused little increase in MHC or costimulatory molecule expression in the CD11b-/low DC but caused upregulated expression in the CD11b+ cells."

"In HIV-infected individuals," concluded Patterson, "there was a marked decrease in the viability of cultured blood mDC, a failure to differentiate into the two populations described for normal donors, and an impaired ability to stimulate T cell proliferation."

Patterson and colleagues published their study in the Journal of Immunology (Human BDCA-1-positive blood dendritic cells differentiate into phenotypically distinct immature and mature populations in the absence of exogenous maturational stimuli: Differentiation failure in HIV infection. J Immunol. 2005 Jun 15;174(12):8200-9.

For more information, contact S. Patterson, Chelsea & Westminster Hospital, Imperial College, Dept. Immunology, 369 Fulham Rd., London SW10 9NH, England.

Publisher contact information for the Journal of Immunology is: American Association Immunologists, 9650 Rockville Pike, Bethesda, MD 20814, USA.

Keywords: London, England, HIV/AIDS, Myeloid Dendritic Cells, Cell Culture, T Cell Proliferation, Differentiation Failure.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Patterson S, Donaghy H, Amjadi P., et al. Human BDCA-1-positive blood dendritic cells differentiate into phenotypically distinct immature and mature populations in the absence of exogenous maturational stimuli: differentiation failure in HIV infection, J Immunol. 2005 Jun 15;174(12):8200-9.

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