Abstract
The release of cytokines by T cells strongly defines their
functional activity in vivo. The ability to produce multiple cytokines
has been associated with beneficial immune responses
in cancer and infectious diseases, while their progressive loss is
associated to T cell exhaustion, senescence and anergy. Consequently,
strategies that enhance the multifunctional status of T
cells are key for immunotherapy. Dendritic cells (DCs) are
professional antigen presenting cells that regulate T cell functions
by providing positive and negative co-stimulatory signals.
A key negative regulator of T cell activity is provided by
binding of programmed death-1 (PD-1) receptor on activated T
cells, to its ligand PD-L1, expressed on DCs. We investigated the
impact of interfering with PD-L1/PD-1 co-stimulation on the
multifunctionality of T cells, by expression of the soluble extracellular
part of PD-1 (sPD-1) or PD-L1 (sPD-L1) in human
monocyte-derived DCs during antigen presentation. Expression,
secretion and binding of these soluble molecules after
mRNA electroporation were demonstrated. Modification of
DCs with sPD-1 or sPD-L1 mRNA resulted in increased levels of
the co-stimulatory molecule CD80 and a distinct cytokine profile, characterized by the secretion of IL-10 and TNF-a, respectively.
Co-expression in DCs of sPD-1 and sPD-L1 with
influenza virus nuclear protein 1 (Flu NP1) stimulated Flu NP1
memory T cells, with a significantly higher number of multifunctional
T cells and increased cytokine secretion, while it did
not induce regulatory T cells. These data provide a rationale for
the inclusion of interfering sPD-1 or sPD-L1 in DC-based immunotherapeutic
strategies
Original language | English |
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Pages (from-to) | 166-167 |
Journal | Human Gene Therapy |
Volume | 24 |
Issue number | 12 |
Publication status | Published - 1 Dec 2013 |
Event | The European Society for Gene and Cell Therapy and the Spanish Society for Gene and Cell Therapy Collaborative Congress 2013 - Madrid, Spain Duration: 25 Oct 2013 → 28 Oct 2013 |
Keywords
- PD-L1/PD-1
- antigen
- dendritic cell