PMID- 24401835
OWN - NLM
STAT- MEDLINE
DCOM- 20141107
LR  - 20240104
IS  - 1476-5462 (Electronic)
IS  - 0969-7128 (Linking)
VI  - 21
IP  - 3
DP  - 2014 Mar
TI  - Interference with PD-L1/PD-1 co-stimulation during antigen presentation enhances 
      the multifunctionality of antigen-specific T cells.
PG  - 262-71
LID - 10.1038/gt.2013.80 [doi]
AB  - 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 with T-cell exhaustion, senescence and anergy. 
      Consequently, strategies that enhance the multifunctional status of T cells are a 
      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-alpha, 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.
FAU - Pen, J J
AU  - Pen JJ
AD  - Laboratory of Molecular and Cellular Therapy, Department of 
      Immunology-Physiology, Vrije Universiteit Brussel, Brussels, Belgium.
FAU - Keersmaecker, B D
AU  - Keersmaecker BD
AD  - Laboratory of Molecular and Cellular Therapy, Department of 
      Immunology-Physiology, Vrije Universiteit Brussel, Brussels, Belgium.
FAU - Heirman, C
AU  - Heirman C
AD  - Laboratory of Molecular and Cellular Therapy, Department of 
      Immunology-Physiology, Vrije Universiteit Brussel, Brussels, Belgium.
FAU - Corthals, J
AU  - Corthals J
AD  - Laboratory of Molecular and Cellular Therapy, Department of 
      Immunology-Physiology, Vrije Universiteit Brussel, Brussels, Belgium.
FAU - Liechtenstein, T
AU  - Liechtenstein T
AD  - 1] Division of Infection and Immunity, Rayne Institute, University College 
      London, London, UK [2] Navarrabiomed-FMS, Complejo Hospitalario de Navarra, 
      Pamplona, Spain.
FAU - Escors, D
AU  - Escors D
AD  - 1] Division of Infection and Immunity, Rayne Institute, University College 
      London, London, UK [2] Navarrabiomed-FMS, Complejo Hospitalario de Navarra, 
      Pamplona, Spain.
FAU - Thielemans, K
AU  - Thielemans K
AD  - Laboratory of Molecular and Cellular Therapy, Department of 
      Immunology-Physiology, Vrije Universiteit Brussel, Brussels, Belgium.
FAU - Breckpot, K
AU  - Breckpot K
AD  - Laboratory of Molecular and Cellular Therapy, Department of 
      Immunology-Physiology, Vrije Universiteit Brussel, Brussels, Belgium.
LA  - eng
PT  - Journal Article
DEP - 20140109
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (B7 Antigens)
RN  - 0 (B7-1 Antigen)
RN  - 0 (Nucleocapsid Proteins)
RN  - 0 (Nucleoproteins)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Viral Proteins)
RN  - 0 (human parainfluenza virus type 1 nucleoprotein)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - *Antigen Presentation
MH  - B7 Antigens/genetics/*immunology/metabolism
MH  - B7-1 Antigen/genetics/metabolism
MH  - Dendritic Cells/*immunology/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Interleukin-10/genetics/metabolism
MH  - Nucleocapsid Proteins
MH  - Nucleoproteins/genetics/metabolism
MH  - Programmed Cell Death 1 Receptor/genetics/*immunology/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - T-Lymphocytes/*immunology/metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
MH  - Viral Proteins/genetics/metabolism
EDAT- 2014/01/10 06:00
MHDA- 2014/11/08 06:00
CRDT- 2014/01/10 06:00
PHST- 2013/02/21 00:00 [received]
PHST- 2013/10/02 00:00 [revised]
PHST- 2013/11/25 00:00 [accepted]
PHST- 2014/01/10 06:00 [entrez]
PHST- 2014/01/10 06:00 [pubmed]
PHST- 2014/11/08 06:00 [medline]
AID - gt201380 [pii]
AID - 10.1038/gt.2013.80 [doi]
PST - ppublish
SO  - Gene Ther. 2014 Mar;21(3):262-71. doi: 10.1038/gt.2013.80. Epub 2014 Jan 9.