| Exploiting cross-priming to generate protective CD8 T-cell immunity rapidly. | |
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MedLine Citation:
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PMID: 20616089 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The number of memory CD8 T cells generated by infection or vaccination correlates strongly with the degree of protection observed in infection and tumor models. Therefore, rapid induction of protective numbers of effector and memory CD8 T cells may be crucial in the case of malignancy, pandemic infection, or bioterrorism. Many studies have shown that amplifying T-cell numbers by prime-boost vaccination is most effective with a substantial time interval between immunizations. In contrast, immunization with peptide-coated mature dendritic cells (DCs) results in a CD8 T-cell response exhibiting accelerated acquisition of memory characteristics, including the ability to respond to booster immunization within days of initial priming. However, personalized DC immunization is too costly, labor intensive, and time-consuming for large-scale vaccination. Here, we demonstrate that in vivo cross-priming with cell-associated antigens or antigen-coated, biodegradable microspheres in the absence of adjuvant quickly generates CD8 T cells that display the phenotype and function of long-term memory populations. Importantly, cross-primed CD8 T cells can respond to booster immunization within days of the initial immunization to generate rapidly large numbers of effector and memory T cells that can protect against bacterial, viral, and parasitic infections, including lethal influenza and malaria-causing Plasmodium infection. Thus, accelerated CD8 T-cell memory after in vivo cross-priming in the absence of adjuvant is generalizable and can be exploited to generate protective immunity rapidly. |
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Authors:
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Nhat-Long L Pham; Lecia L Pewe; Courtney J Fleenor; Ryan A Langlois; Kevin L Legge; Vladimir P Badovinac; John T Harty |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-06-21 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 107 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-09 Completed Date: 2010-08-30 Revised Date: 2011-11-21 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 12198-203 Citation Subset: IM |
Affiliation:
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Departments of Microbiology, University of Iowa, Iowa City, IA 52242, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals CD8-Positive T-Lymphocytes / cytology, immunology*, metabolism Cross-Priming / immunology* Dendritic Cells / immunology Immunity / immunology* Immunization / methods Immunization, Secondary Immunologic Memory / immunology* Leukocytes, Mononuclear / immunology Listeria monocytogenes / immunology Listeriosis / immunology, microbiology Malaria / immunology, parasitology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Transgenic Models, Immunological Ovalbumin / immunology Plasmodium berghei / immunology Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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AI150073/AI/NIAID NIH HHS; AI42767/AI/NIAID NIH HHS; AI46653/AI/NIAID NIH HHS; AI83286/AI/NIAID NIH HHS; R01 AI050073-10/AI/NIAID NIH HHS; R37 AI042767-14/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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9006-59-1/Ovalbumin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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