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Published on: August 1, 2013
Chimpanzee dendritic cells with potent immunostimulatory function can be propagated from peripheral blood
S M Barratt-Boyes1, R A Henderson, O J Finn
1Department of Molecular Genetics and Biochemistry, School of Medicine, University of Pittsburgh, PA, USA.
Insights
Researchers developed dendritic cell (DC) cultures from chimpanzee blood, yielding significantly more cells than human cultures. These chimpanzee DCs effectively present antigens, offering a valuable model for human disease research, including cancer immunotherapy and HIV pathogenesis.
Area of Science:
- Immunology
- Primate research
Background:
- Dendritic cells (DCs) are crucial antigen-presenting cells in the immune system.
- Establishing reliable DC cultures is essential for immunological studies and therapeutic development.
Purpose of the Study:
- To establish and characterize dendritic cell (DC) cultures from chimpanzee peripheral blood mononuclear cells (PBMC).
- To evaluate the antigen-presenting capacity of chimpanzee DCs.
- To assess the potential of chimpanzee DCs as a model for human disease research.
Main Methods:
- Chimpanzee PBMCs were cultured using recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) and rh interleukin-4 (IL-4).
- DC characteristics were assessed through morphology, immunophenotyping (CD83, MHC class II, adhesion, costimulatory molecules), and functional assays (mixed leukocyte response, antigen presentation).
Main Results:
- High yields of chimpanzee DCs (5% of PBMC) were obtained, significantly exceeding human DC yields.
- Cultured chimpanzee DCs exhibited typical DC morphology and expressed key markers like CD83 and high levels of MHC class II.
- Chimpanzee DCs demonstrated potent allogeneic mixed leukocyte responses and efficiently presented tetanus toxoid to CD4+ T cells.
Conclusions:
- Chimpanzee DCs generated ex vivo closely resemble human blood-derived DCs.
- This methodology provides a robust primate model for studying DC function and potential immunotherapeutics.
- Chimpanzee DCs can be utilized to investigate cancer immunotherapy and the pathogenesis of human immunodeficiency virus (HIV) infection.
Abstract:
We have established dendritic cell (DC) cultures from chimpanzee peripheral blood mononuclear cells (PBMC) by using recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) and rh interleukin-4 (IL-4) and demonstrate that these cells have all the characteristics of DC as described for other species. We consistently can obtain 1 x 10(7) DC per 100 ml of blood, a yield of 5% DC as compared to 0.1 to 0.5% DC reported in fresh human PBMC. The cultured DC have a varied morphology with typical cytoplasmic extensions. Phenotypically, the blood-derived DC lack expression of most lineage antigens, but express CD83, an antigen specifically expressed on human blood DC. Chimpanzee DC express very high levels of major histocompatability complex class II antigens, adhesion and costimulatory molecules. Consistent with this phenotype of a powerful antigen-presenting cell, chimpanzee DC generate allogeneic mixed leukocyte responses 15 to 20 times more potent than that elicited by macrophages, Epstein-Barr virus-transformed lymphoblasts and fresh PBMC. In addition, chimpanzee DC very efficiently present tetanus toxoid to PBMC-derived CD4+ T cells as compared to macrophages and PBMC. The DC generated by culturing chimpanzee PBMC with rhGM-CSF and rhIL-4 thus closely resemble human blood-derived DC propagated in the same manner. This technology provides a powerful animal model with which to apply DC to clinical studies with relevance to human disease. In particular, chimpanzee DC can be tested as immunotherapeutic agents for cancer, and be studied in relation to the pathogenesis of human immunodeficiency virus (HIV) infection.
