Synergy between rapamycin and FLT3 ligand enhances plasmacytoid dendritic cell-dependent induction of CD4+CD25+FoxP3+ Treg
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Key Points: Rapamycin and Flt3L are synergistic in Treg induction when coadministered with antigen, resulting in improved tolerance induction. pDCs are required for efficient Treg induction and selectively expanded with Flt3L/rapamycin because of high mTOR activity.
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Increased levels of gene expression resulting from higher vector doses promote immune tolerance through elevated expression of IL-10, enhanced apoptosis of effector T cells, and enhanced Treg induction.
“However, the exact opposite is true, and increased levels of gene expression resulting from higher vector doses promote immune tolerance through elevated expression of the immune suppressive cytokine IL-10, enhanced apoptosis of effector T cells, and enhanced Treg induction similar to that observed with a very high HBV inoculum in chimpanzees.15,56,57,58,59,60,61,62”
From TLR9-independent CD8+ T cell responses in hepatic AAV gene transfer through IL-1R1-MyD88 signaling (2024) · cites this paper as [56]
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References 57 · Cited by 70
- Authors
- Biswas, M., Sarkar, D., Kumar, S. R. P., Nayak, S., Rogers, G. L., Markusic, D. M., Liao, G., Terhorst, C., & Herzog, R. W.
- Affiliations
- University of Florida Health (US)
- Beth Israel Deaconess Medical Center (US)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2015-05-07
- Volume
- 125
- Issue
- 19
- Pages
- 2937-2947
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC4424416
- OpenAlex
- W2036757808
- Cited by
- 70
- References
- 57
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 11 · 2019: 6 · 2018: 10 · 2017: 8 · 2016: 9 · 2015: 4
- FWCI
- 5.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Florida
- Celldex Therapeutics
- National Institutes of Health
- University of Florida Health
- National Heart, Lung, and Blood Institute (P01HL078810)
- National Institute of Allergy and Infectious Diseases (R01AI051390, R01 AI51390, T32AI007110)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK052510)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- rapamycin, Flt3 ligand, plasmacytoid dendritic cells, regulatory T cells, Foxp3, mTOR signaling, Treg induction, immune tolerance, antigen-specific tolerance, gene therapy, protein therapy, CD8+ T cell responses, antibody response, dendritic cell subsets
- MeSH terms
- Animals, Antibiotics, Antineoplastic, Cells, Cultured, Dendritic Cells, Drug Synergism, Flow Cytometry, Humans, Immune Tolerance, Male, Membrane Proteins, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Phosphorylation, Blotting, Western, Signal Transduction, CD4-Positive T-Lymphocytes, Cytokines, Apoptosis, Sirolimus, T-Lymphocytes, Regulatory, Mice, Forkhead Transcription Factors, Interleukin-2 Receptor alpha Subunit, TOR Serine-Threonine Kinases
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