Human B cells that hyperexpress a triad of costimulatory molecules via avipox-vector infection: an alternative source of efficient antigen-presenting cells.
Dendritic cells (DCs) are the most potent of the antigen-presenting cells (APCs). Preparation of sufficient numbers of mature DCs, however, is both costly and time-consuming. We have examined here the possibility of using an alternative source of APCs that would be easier to obtain, would not require extensive culture, and thus would be more applicable to human immunotherapy protocols. We show here that freshly isolated human B cells can be efficiently infected by a replication-defective fowlpox recombinant vector, designated rF-TRICOM (TRIad of COstimulatory Molecules), to markedly increase surface expression of the human costimulatory molecule B7-1 and moderately increase expression of intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-3 (LFA-3). Peptide-pulsed rF-TRICOM-infected B cells were highly efficient in activating antigen-specific human T cells and shown to be superior to the use of CD40L in enhancing APC potency. Moreover, when infection of freshly isolated B cells with rF-TRICOM was combined with CD40L, a still further marked enhancement of the antigen-presenting potency was observed. Ex vivo-generated antigen-specific T cells activated in this manner might be applied to experimental protocols or used for adoptive transfer in immunotherapy protocols.
Palena
Claudia
C
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Zhu
MingZhu
M
Schlom
Jeffrey
J
Tsang
Kwong-Yok
KY
D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D018968:CD58 Antigens / Q000096:biosynthesis* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000276:immunology; D002460:Cell Line; D005587:Fowlpox virus / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology; D027383:Papillomaviridae / Q000276:immunology; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D017430:Prostate-Specific Antigen / Q000276:immunology; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism
D018122:B7-1 Antigen; D018968:CD58 Antigens; D002272:Carcinoembryonic Antigen; D010455:Peptides; D014764:Viral Proteins; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand; D007371:Interferon-gamma; D017430:Prostate-Specific Antigen