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Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer.
- Source :
- Frontiers in Immunology; 6/30/2020, p1-14, 14p
- Publication Year :
- 2020
-
Abstract
- The prominent role of dendritic cells (DC) in promoting tolerance and the development of methods to generate clinical grade products allowed the clinical application of tolerogenic DC (tolDC)-based therapies for controlling unwanted immune responses. We established an efficient method to generate tolerogenic human DC, producing supra-physiological levels of IL-10, by genetically engineering monocyte-derived DC with a bidirectional Lentiviral Vector (bdLV) encoding for IL-10 and a marker gene. DC<superscript>IL−10</superscript> are mature DC, modulate T cell responses, promote T regulatory cells, and are phenotypically and functionally stable upon stimulation. Adoptive transfer of human DC<superscript>IL−10</superscript> in a humanized mouse model dampens allogeneic T cell recall responses, while murine DC<superscript>IL−10</superscript> delays acute graft-vs.-host disease in mice. Our report outlines an efficient method to transduce human myeloid cells with large-size LV and shows that stable over-expression of IL-10 generates an effective cell product for future clinical applications in the contest of allogeneic transplantation. [ABSTRACT FROM AUTHOR]
- Subjects :
- DENDRITIC cells
GENETIC transformation
SUPPRESSOR cells
T cells
MOUSE diseases
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Database :
- Complementary Index
- Journal :
- Frontiers in Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 144340599
- Full Text :
- https://doi.org/10.3389/fimmu.2020.01260