CpG-C Immunostimulatory Oligodeoxyribonucleotide Activation of Plasmacytoid Dendritic Cells in Rhesus Macaques to Augment the Activation of IFN-γ-Secreting Simian Immunodeficiency Virus-Specific T Cells
| Autor: | Jeffrey D. Lifson, Rudolf P. Bohm, Jason Marshall, Jessica Kenney, Gary Van Nest, Jason Dufour, Melissa Pope, Agegnehu Gettie, Jennifer Jones, Natalia Teleshova |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
T cell Immunology Interleukin-3 Receptor alpha Subunit Oligonucleotides chemical and pharmacologic phenomena Lymphocyte Activation medicine.disease_cause Macaque Interferon-gamma 2 2'-Dipyridyl Immune system Adjuvants Immunologic T-Lymphocyte Subsets biology.animal medicine Animals Immunology and Allergy Disulfides Cells Cultured CD86 CD40 biology SAIDS Vaccines Interferon-alpha hemic and immune systems Dendritic Cells Simian immunodeficiency virus Acquired immune system Interleukin-12 Macaca mulatta Virology Receptors Interleukin-3 CD11c Antigen medicine.anatomical_structure Oligodeoxyribonucleotides Vaccines Inactivated biology.protein Female Interleukin-3 Simian Immunodeficiency Virus CD80 |
| Zdroj: | The Journal of Immunology. 173:1647-1657 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | There are two principle subsets of dendritic cells (DCs); CD11c+CD123− myeloid DCs (MDCs) and CD11c−CD123+ plasmacytoid DCs (PDCs). DC activation via TNF-TNFRs (e.g., CD40L) and TLRs (e.g., immunostimulatory oligodeoxyribonucleotides (ISS-ODNs)) is crucial for maximal stimulation of innate and adaptive immunity. Macaque DC biology is being studied to improve HIV vaccines using the SIV macaque model. Using lineage (Lin) markers to exclude non-DCs, Lin−HLA-DR+CD11c+CD123− MDCs and Lin−HLA-DR+CD11c−CD123+ PDCs were identified in the blood of uninfected macaques and healthy macaques infected with SIV or simian-human immunodeficiency virus. Overnight culture of DC-enriched Lin-depleted cells increased CD80 and CD86 expression. IL-12 production and CD80/CD86 expression by MDC/PDC mixtures was further enhanced by CD40L and ISS-ODN treatment. A CpG-B ISS-ODN increased CD80/CD86 expression by PDCs, but resulted in little IFN-α secretion unless IL-3 was added. In contrast, a CpG-C ISS-ODN and aldrithiol-2-inactivated (AT-2) SIV induced considerable PDC activation and IFN-α release without needing exogenous IL-3. The CpG-C ISS-ODN also stimulated IL-12 release (unlike AT-2 SIV) and augmented DC immunostimulatory activity, increasing SIV-specific T cell IFN-γ production induced by AT-2 SIV-presenting MDC/PDC-enriched mixtures. These data highlight the functional capacities of MDCs and PDCs in naive as well as healthy, infected macaques, revealing a promising CpG-C ISS-ODN-driven DC activation strategy that boosts immune function to augment preventative and therapeutic vaccine efficacy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|