Plasmacytoid dendritic cells prime IFN-gamma-secreting melanoma-specific CD8 lymphocytes and are found in primary melanoma lesions.
Plasmacytoid dendritic cells (PDC) are a small population of leukocytes specialized in the production of type I IFN. It has been shown that PDC have a potent T cell stimulatory capacity in allogeneic mixed lymphocyte reaction, However, their role in initiating primary immune responses remains elusive. We report that blood PDC efficiently prime naive CD8(+) lymphocytes specific for the melan-A(26-35) epitope to become IFN-gamma producing cells in vitro. In addition, we found that CD40L-stimulated PDC induce expression on primed melan-A-specific T cells of cutaneous lymphocyte antigen and L-selectin (CD62L), homing receptors that allow the migration of effector cells to the inflamed skin. Finally, we show that PDC can be found in the peri-tumoral area of most primary cutaneous melanomas in vivo and that type I IFN-containing supernatants derived from PDC increase melanoma cell surface expression of CD95 and MHC class I and class II molecules in vitro. Our results suggest a new immunomodulatory role for tissue infiltrating PDC, which may prime tumor-specific T cell responses and affect tumor growth via soluble factors.
Salio
Mariolina
M
Tumor Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, GB. msalio@molbiol.ox.ac.uk
Cella
Marina
M
Vermi
William
W
Facchetti
Fabio
F
Palmowski
Michael J
MJ
Smith
Caroline L
CL
Shepherd
Dawn
D
Colonna
Marco
M
Cerundolo
Vincenzo
V
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000096:biosynthesis; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000494:pharmacology; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000276:immunology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000096:biosynthesis
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D006649:Histocompatibility Antigens; D007370:Interferon Type I; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D019014:fas Receptor; D018664:Interleukin-12; D007371:Interferon-gamma