Back to Search
Start Over
IL-12p40-overexpressing immature dendritic cells induce T cell hyporesponsiveness in vitro but accelerate allograft rejection in vivo: role of NK cell activation and interferon-gamma production
- Source :
-
Immunology Letters . Jul2004, Vol. 94 Issue 3, p191-199. 9p. - Publication Year :
- 2004
-
Abstract
- Infusion of genetically modified dendritic cells (DC) expressing immunosuppressive molecules is a potential therapy for organ rejection. IL-12p70, a cytokine produced mainly by DC and macrophages, consists of two subunits, p40 and p35. IL-12p70 is an activator of T cells, while the IL-12p40 subunit serves as a natural antagonist for IL-12p70 action. The primary aim of this study was to evaluate the effect of IL-12p40 gene-modification on both the T-cell stimulatory activity of immature DC (imDC) and their ability to prolong cardiac allograft survival. IL-12p40 gene-modified imDC (DC-p40) exhibited a phenotype characteristic of imDC and displayed impaired T-cell allostimulatory ability in vitro. However, to our surprise, for murine vascularized heterotopic heart transplantation (HHT), administration of donor-derived DC-p40 7 days prior to transplantation did not prolong allograft survival but instead significantly exacerbated cardiac allograft rejection. Further study showed that DC-p40 augmented NK cell activity both in vitro and in vivo and enhanced interferon-gamma (IFN-γ) production in vivo, which might be due to the increased IL-23 production by DC-p40. Our data suggested that although IL-12p40 gene-modified immature DC can induce T cell hyporesponsiveness in vitro, their ability to activate NK cells and induce IFN-γ production counterbalances this, exacerbating cardiac allograft rejection. The unexpected effects of DC-p40 limit their value in promoting allograft survival in vivo and likely reflect the complexity of IL-12p40 biology. [Copyright &y& Elsevier]
- Subjects :
- *CELLS
*EXPERTISE
*GENETICS
*MOLECULES
Subjects
Details
- Language :
- English
- ISSN :
- 01652478
- Volume :
- 94
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Immunology Letters
- Publication Type :
- Academic Journal
- Accession number :
- 13904359
- Full Text :
- https://doi.org/10.1016/j.imlet.2004.05.001