Plasmacytoid dendritic cell precursors induce allogeneic T-cell hyporesponsiveness and prolong heart graft survival.
Dendritic cell (DC) precursors were propagated from C57BL/10 (B10; H2b) mouse bone marrow in fms-like tyrosine kinase 3 ligand. Cosignaling molecule (B7-1/B7-2 and B7-H1) expression and stimulatory capacity of precursor (pre)-plasmacytoid (p)DC (CD11c+B220+CD11b-CD19-) and classic myeloid DC (MDC) for allogeneic (C3H; H2k) T cells were compared. Unstimulated pre-pDC exhibited very low levels of surface MHC class II and classic costimulatory molecules (B7-1/B7-2), whereas a minor population expressed B7-H1 at levels higher than on MDC. The pre-pDC were ineffective T-cell stimulators and induced nonspecific hyporesponsiveness to rechallenge with donor alloantigens in vitro and in vivo. Following stimulation with CpG-oligonucleotide (CpG-ODN), B7 molecule expression was upregulated on pre-pDC, however the ratio between coinhibitory (B7-H1) and costimulatory (B7-1/B7-2) signals was much higher (five- to six-fold) on pre-pDC than MDC. Blockade of B7-H1 expression on pDC increased their T-cell allostimulatory capacity significantly. A single preoperative infusion of C3H hosts with pre-pDC prolonged B10 heart graft survival significantly but nonspecifically compared with untreated mice (median survival times 22 vs. 9 days, respectively). Thus, pre-pDC of donor origin have potential to regulate T-cell responses to alloantigens and can prolong organ graft survival.
Thomas E Starzl Transplantation Institute and Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Masanori
M
Abe
Zhiliang
Z
Wang
An
A
de Creus
Angus W
AW
Thomson
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D060890:B7-H1 Antigen; D001854:Bone Marrow Cells / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006084:Graft Rejection; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010455:Peptides / Q000037:antagonists & inhibitors / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060890:B7-H1 Antigen; C408982:CPG-oligonucleotide; C498919:Cd274 protein, mouse; C497965:Cd86 protein, mouse; D007519:Isoantigens; D008024:Ligands; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D011505:Protein-Tyrosine Kinases