Publication Date:
2012-12-21
Description:
The reactivation of human cytomegalovirus (HCMV) poses a serious health threat to immune compromised individuals. As a treatment strategy, dendritic cell (DC) vaccination trials are ongoing. Recent work suggests that BDCA-3 + (CD141 + ) subset DCs may be particularly effective in DC vaccination trials. BDCA-3 + DCs had however been mostly characterized for their ability to cross-present antigen from necrotic cells. We here describe our study of human BDCA-3 + DCs in elicitation of HCMV-specific CD8 + T-cell clones. We show that Fcgamma-receptor (FcR) antigen targeting facilitates antigen cross-presentation in several DC subsets, including BDCA-3 + DCs. FcR antigen targeting stimulates antigen uptake by BDCA-1 + rather than BDCA-3 + DCs. Conversely, BDCA-3 + DCs and not BDCA-1 + DCs show improved cross-presentation by FcR targeting, as measured by induced release of IFN and TNF by antigen-specific CD8 + T cells. FcR-facilitated cross-presentation requires antigen processing in both an acidic endosomal compartment and by the proteasome, and did not induce substantial DC maturation. FcRII is the most abundantly expressed FcR on both BDCA-1 + and BDCA-3 + DCs. Furthermore we show that BDCA-3 + DCs express relatively more stimulatory FcRIIa than inhibitory FcRIIb in comparison with BDCA-1 + DCs. These studies support the exploration of FcR antigen targeting to BDCA-3 + DCs for human vaccination purposes.
Keywords:
Immunobiology
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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