Adenoviral-encoded antigens are presented efficiently by a subset of dendritic cells expressing high levels of αvβ3 integrins
| Autor: | Airi Harui, Michael D. Roth, Saroj K. Basak, Mihir Sanghvi, Darshni Vira, Hiroyuki Mizuguchi |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Ovalbumin T cell Genetic Vectors Immunology Integrin Antigen presentation Bone Marrow Cells Major histocompatibility complex Adenoviridae Mice Antigen Transduction Genetic MHC class I medicine Animals Immunology and Allergy Transgenes Antigens Viral Interleukin 4 Antigen Presentation biology H-2 Antigens Integrin beta3 Granulocyte-Macrophage Colony-Stimulating Factor Dendritic Cells Cell Biology Integrin alphaV Integrin alphaVbeta3 Virology Molecular biology Recombinant Proteins Mice Inbred C57BL medicine.anatomical_structure B7-1 Antigen biology.protein B7-2 Antigen Interleukin-4 Oligopeptides Spleen CD8 |
| Zdroj: | Journal of Leukocyte Biology. 79:1271-1278 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1189/jlb.1105694 |
| Popis: | Dendritic cells (DC) play a central role in antigen presentation and are often targeted by adenoviral (Ad)-based gene therapy. However, DC lack the coxsackie-Ad receptor, and little is known about the process by which they acquire and present Ad-encoded antigens. We examined the expression of ανβ3 integrins (CD51/CD61) on mouse bone marrow-derived DC (BM-DC) and their susceptibility to transduction by Ad vectors. Less than 10% of BM-DC precursors expressed CD51, but expression increased over time in culture with granulocyte macrophage-colony stimulating factor (GM-CSF)/interleukin (IL)-4. After 7 days, 28 ± 1.7% of CD11c+ DC expressed high levels of CD51 (CD51hi), and the remaining DC expressed low levels of CD51 (CD51lo). CD51hi CD express higher major histocompatibility complex type 1 (MHC I); however, both of the DC subsets expressed similar levels of MHC II and costimulatory molecules. When exposed to a first-generation Ad vector, transgene expression was restricted to the CD51hi DC subset and blocked by soluble peptides expressing an arginine, glycine, aspartic acid (RGD) sequence, confirming the role of integrins in viral entry. Consistent with this, a modified Ad expressing an RGD-binding sequence in its fiber knob (Ad-RGD) transduced the CD51hi DC subset with significantly higher efficiency. When BM-DC were transduced with an Ad-expressing ovalbumin (Ad-OVA), the CD51hi subset proved superior in activating OT-I (T cell receptor-OVA) T cells. Similar to in vitro effects, systemic administration of GM-CSF/IL-4 increased the expression of CD51 on splenic DC and rendered these cells susceptible to Ad transduction. These results suggest that a limited subset of DC expressing high levels of ανβ3 integrins is preferentially transduced by Ad vectors and activates CD8+ T cell responses against Ad-encoded antigens. |
| Databáze: | OpenAIRE |
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