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Antigen presentation by MART‐1 adenovirus‐transduced interleukin‐10‐polarized human monocyte‐derived dendritic cells
Author(s) -
Mehrotra Shikhar,
Chhabra Arvind,
Chakraborty Abolokita,
Chattopadhyay Subhasis,
Slowik Mark,
Stevens Robert,
Zengou Ryan,
Mathias Clinton,
Butterfield Lisa H.,
Dorsky David I.,
Economou James S.,
Mukherji Bijay,
Chakraborty Nitya G.
Publication year - 2004
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2004.01978.x
Subject(s) - epitope , antigen presentation , antigen , biology , immune system , major histocompatibility complex , antigen presenting cell , cytotoxic t cell , dendritic cell , cd8 , t cell , monocyte , mhc class i , cross presentation , antigen processing , mhc class ii , microbiology and biotechnology , immunology , in vitro , biochemistry
Summary 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.