A distinct subset of plasmacytoid dendritic cells induces activation and differentiation of B and T lymphocytes.
Plasmacytoid dendritic cells (pDCs) are known mainly for their secretion of type I IFN upon viral encounter. We describe a CD2hiCD5+CD81+pDC subset, distinguished by prominent dendrites and a mature phenotype, in human blood, bone marrow, and tonsil, which can be generated from CD34+progenitors. These CD2hiCD5+CD81+cells express classical pDC markers, as well as the toll-like receptors that enable conventional pDCs to respond to viral infection. However, their gene expression profile is distinct, and they produce little or no type I IFN upon stimulation with CpG oligonucleotides, likely due to their diminished expression of IFN regulatory factor 7. A similar population of CD5+CD81+pDCs is present in mice and also does not produce type I IFN after CpG stimulation. In contrast to conventional CD5-CD81-pDCs, human CD5+CD81+pDCs are potent stimulators of B-cell activation and antibody production and strong inducers of T-cell proliferation and Treg formation. These findings reveal the presence of a discrete pDC population that does not produce type I IFN and yet mediates important immune functions previously attributed to all pDCs.
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94304.
Hong
H
Zhang
Kyowa Kirin Pharmaceutical Research, La Jolla, CA 92037.
Josh D
JD
Gregorio
Soulage Medical Clinic, Inage-Ku Chiba-City, Chiba, 263-0005, Japan.
Toru
T
Iwahori
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94304.
Xiangyue
X
Zhang
Stanford Blood Center, Stanford Hospital, Stanford, CA 94304.
Okmi
O
Choi
Stanford Blood Center, Stanford Hospital, Stanford, CA 94304.
Lorna L
LL
Tolentino
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94304.
Tyler
T
Prestwood
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94304.
Yaron
0000-0002-0972-0616
Y
Carmi
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94304; edengleman@stanford.edu.
Edgar G
EG
Engleman
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D018801:CD2 Antigens / Q000378:metabolism; D018956:CD5 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000502:physiology*; D002469:Cell Separation; D003713:Dendritic Cells / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*; D060225:Tetraspanin 28 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism
D018801:CD2 Antigens; D018956:CD5 Antigens; C408982:CPG-oligonucleotide; D007370:Interferon Type I; D009838:Oligodeoxyribonucleotides; D060225:Tetraspanin 28; D051193:Toll-Like Receptors
CD2; CD5; CD81; plasmacytoid dendritic cells; type I IFN