Lentiviral vector-transduced dendritic cells induce specific T cell response in a nonhuman primate model.
Dendritic cells (DCs) are effective in stimulating and controlling the outcome of T cell responses. Human immunodeficiency virus type 1-based lentiviral vectors can achieve sustained transduction of genes/antigens in dividing and nondividing cells, thus representing a candidate vector for stable expression of antigens in DCs. We previously established conditions for transduction of purified cytokine mobilized rhesus CD34(+) cells in vitro, and transplantation of the autologous transduced cells in a nonhuman primate model in vivo. In the present study, we transplanted DCs derived from EGFP-transduced CD34(+) cells into nonmyeloablated rhesus macaques. Transplantation of DCs stably expressing EGFP into autologous animals induces persistent, long-lived (up to 100 weeks) EGFP-specific T cell responses. Of note, no humoral responses against EGFP are detected in the transplanted animals. These studies provide, to our knowledge, the first demonstration that lentiviral transduction of CD34(+) progenitor cells subsequently differentiated to DCs is capable of priming a specific T cell response in a nonhuman primate in vivo. Taken together, our data provide formal in vivo evidence that lentivirus-transduced dendritic cells represent a potential approach in eliciting cellular immune responses in primates.
Kung
Sam K P
SK
Department of Microbiology and Immunology and Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
Bonifacino
Aylin
A
Metzger
Mark E
ME
Ringpis
Gene-Errol
GE
Donahue
Robert E
RE
Chen
Irvin S Y
IS
D000818:Animals; D000917:Antibody Formation; D018952:Antigens, CD34 / Q000235:genetics / Q000276:immunology; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D005822:Genetic Vectors / Q000009:adverse effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007106:Immune Sera; D007371:Interferon-gamma / Q000494:pharmacology; D016086:Lentivirus / Q000235:genetics*; D008253:Macaca mulatta; D011323:Primates; D013234:Stem Cells / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D014161:Transduction, Genetic / Q000379:methods*
D018952:Antigens, CD34; D007106:Immune Sera; D049452:Green Fluorescent Proteins; D007371:Interferon-gamma