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Blood, 15 December 2003, Vol. 102, No. 13, pp. 4487-4492.
Prepublished online as a Blood First Edition Paper on August 28, 2003; DOI 10.1182/blood-2003-07-2465.


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IMMUNOBIOLOGY

IL-10 regulates plasmacytoid dendritic cell response to CpG-containing immunostimulatory sequences

Omar Duramad, Karen L. Fearon, Jean H. Chan, Holger Kanzler, Jason D. Marshall, Robert L. Coffman, and Franck J. Barrat

From the Dynavax Technologies Corporation, Berkeley, CA.

Immunostimulatory sequences (ISS) are short oligonucleotides containing unmethylated cytosine-phosphate-guanine (CpG) dinucleotides that stimulate innate immune responses through Toll-like receptor-9 on B cells and plasmacytoid dendritic cell (PDC) precursors. The anti-inflammatory cytokine interleukin (IL)-10 is predicted to be a potent inhibitor of many of the activities described for ISS, and this may impact the use of ISS in disease states characterized by elevated IL-10. As the activities of ISS on PDCs are central to many clinical applications of ISS, we have studied the effects of IL-10 on PDC stimulation by 3 distinct classes of ISS. IL-10 inhibited cytokine production and survival of ISS-activated PDCs; however, IL-12 induction was much more sensitive to inhibition than interferon (IFN)-{alpha} induction. Within the PDC population are cells that respond to ISS by producing either IL-12 or IFN-{alpha} but not both cytokines. IL-12-producing PDCs require costimulation through CD40 and appear more mature than IFN-{alpha}-producing PDCs. The 3 distinct classes of ISS differed with respect to induction of PDC maturation and T-cell priming capacity. IL-10 regulated PDC activation but did not inhibit the subsequent T-cell-priming ability of PDCs already activated by ISS. (Blood. 2003;102:4487-4492)


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