Mature human Langerhans cells derived from CD34+ hematopoietic progenitors stimulate greater cytolytic T lymphocyte activity in the absence of bioactive IL-12p70, by either single peptide presentation or cross-priming, than do dermal-interstitial or monocyte-derived dendritic cells.
The emerging heterogeneity of dendritic cells (DCs) mirrors their increasingly recognized division of labor at myriad control points in innate and acquired cellular immunity. We separately generated blood monocyte-derived DCs (moDCs), as well as Langerhans cells (LCs) and dermal-interstitial DCs (DDC-IDCs) from CD34(+) hematopoietic progenitor cells. Differential expression of CD11b, CD52, CD91, and the CD1 isoforms proved useful in distinguishing these three DC types. All mature DCs uniformly expressed comparable levels of HLA-DR, CD83, CD80, and CD86, and were potent stimulators of allogeneic T cells after exposure either to recombinant human CD40L trimer or a combination of inflammatory cytokines with PGE(2). moDCs, however, required 0.5-1 log greater numbers than LCs or DDC-IDCs to stimulate comparable T cell proliferation. Only moDCs secreted the bioactive heterodimer IL-12p70, and moDCs phagocytosed significantly more dying tumor cells than did either LCs or DDC-IDCs. LCs nevertheless proved superior to moDCs and DDC-IDCs in stimulating CTL against a recall viral Ag by presenting passively loaded peptide or against tumor Ag by cross-priming autologous CD8(+) T cells. LCs also secreted significantly more IL-15 than did either moDCs or DDC-IDCs, which is especially important to the generation of CTL. These findings merit further comparisons in clinical trials designed to determine the physiologic relevance of these distinctions in activity between LCs and other DCs.
Laboratory of Cellular Immunobiology, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Gudrun
G
Ratzinger
Jan
J
Baggers
Maria A
MA
de Cos
Jianda
J
Yuan
Tao
T
Dao
John L
JL
Reagan
Christian
C
Münz
Glenn
G
Heller
James W
JW
Young
D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D002478:Cells, Cultured; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D020405:Dermis / Q000166:cytology / Q000276:immunology; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D007801:Langerhans Cells / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D018613:Microscopy, Confocal; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D010641:Phenotype; D021122:Protein Subunits / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015703:Antigens, CD; D018952:Antigens, CD34; D006684:HLA-DR Antigens; D021122:Protein Subunits; D018664:Interleukin-12