Antigen presentation by MART-1 adenovirus-transduced interleukin-10-polarized human monocyte-derived dendritic cells.
Dendritic cells (DC) play critical roles in generating an immune response and in inducing tolerance. Diverse microenvironmental factors can 'polarize' DC toward an immunogenic or non-immunogenic phenotype. Among the various microenvironmental factors, interleukin-10 (IL-10) exhibits a potent immunosuppressive effect on antigen-presenting cells (APC). Here, we show that monocyte-derived DC generated in the presence of IL-10 exhibit a profound down-regulation of many genes that are associated with immune activation and show that the IL-10-grown DC are poor stimulators of CD8(+) T cells in a strictly autologous and major histocompatibility complex (MHC) class I-restricted melanoma antigen recognized by T cells (MART-1) epitope presentation system. However, these IL-10-grown DC can efficiently activate the epitope-specific CD8(+) T cells when they are made to present the epitope following transduction with an adenoviral vector expressing the MART-1 antigen. In addition, we show that the MART-1 protein colocalizes with the MHC class I protein, equally well, in the iDC and in the DC cultured in presence of IL-10 when both DC types are infected with the viral vector. We also show that the vector transduced DC present the MART-1(27-35) epitope for a sustained period compared to the peptide pulsed DC. These data suggest that although DCs generated in the presence of IL-10 tend to be non-immunogenic, they are capable of processing and presenting an antigen when the antigen is synthesized within the DC.
Mehrotra
Shikhar
S
Department of Medicine, University of Connecticut School of Medicine, Farmington Avenue, Farmington, CT, USA.
Chhabra
Arvind
A
Chakraborty
Abolokita
A
Chattopadhyay
Subhasis
S
Slowik
Mark
M
Stevens
Robert
R
Zengou
Ryan
R
Mathias
Clinton
C
Butterfield
Lisa H
LH
Dorsky
David I
DI
Economou
James S
JS
Mukherji
Bijay
B
Chakraborty
Nitya G
NG
D000256:Adenoviridae / Q000235:genetics; D017951:Antigen Presentation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005822:Genetic Vectors; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D014161:Transduction, Genetic
D000951:Antigens, Neoplasm; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D016753:Interleukin-10; D007371:Interferon-gamma