Live attenuated yellow fever 17D infects human DCs and allows for presentation of endogenous and recombinant T cell epitopes Journal Article
| Authors: | Barba-Spaeth, G.; Longman, R. S.; Albert, M. L.; Rice, C. M. |
| Article Title: | Live attenuated yellow fever 17D infects human DCs and allows for presentation of endogenous and recombinant T cell epitopes |
| Abstract: | The yellow fever (YF) 17D vaccine is one of the most successful live attenuated vaccines available. A single immunization induces both long-lasting neutralizing antibody and YF-specific T cell responses. Surprisingly, the mechanism for this robust immunity has not been addressed. In light of several recent reports suggesting flavivirus interaction with dendritic cells (DCs), we investigated the mechanism of YF17D interaction with DCs and the importance of this interaction in generating T cell immunity. Our results show that YF17D can infect immature and mature human DCs. Viral entry is Ca2+ dependent, but it is independent of DC-SIGN as well as multiple integrins expressed on the DC surface. Similar to infection of cell lines, YF infection of immature DCs is cytopathic. Although infection itself does not induce DC maturation in vitro, TNF-α-induced maturation protects DCs from YF-induced cytopathogenicity. Furthermore, we show that DCs infected with YF17D or YF17D carrying a recombinant epitope can process and present antigens for CD8+ T cell stimulation. These findings offer insight into the immunologic mechanisms associated with the highly capable YF17D vaccine that may guide effective vaccine design. JEM © The Rockefeller University Press. |
| Keywords: | protein expression; human cell; nonhuman; cd8 antigen; t lymphocyte; t-lymphocytes; cells, cultured; apoptosis; cell maturation; dendritic cell; cell line; calcium; in vitro study; antigen presentation; lymphocyte activation; dendritic cells; cellular immunity; antigen; tumor necrosis factor alpha; epitope; vaccines, synthetic; virus antigen; epitopes, t-lymphocyte; cell interaction; integrin; cytopathogenic effect; live vaccine; cell surface; virus attenuation; calcium ion; vaccines, attenuated; cd209 antigen; yellow fever vaccine; immaturity; yellow fever; yellow fever flavivirus; yellow fever virus |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 202 |
| Issue: | 9 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2005-11-07 |
| Start Page: | 1179 |
| End Page: | 1184 |
| Language: | English |
| DOI: | 10.1084/jem.20051352 |
| PUBMED: | 16260489 |
| PROVIDER: | scopus |
| PMCID: | PMC2213233 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 49" - "Export Date: 24 October 2012" - "CODEN: JEMEA" - "Source: Scopus" |
