Alteration of T cell immunity by lentiviral transduction of human monocyte-derived dendritic cells.
BACKGROUND
Dendritic cells (DCs) are professional antigen-presenting cells that play important roles during human immunodeficiency virus type 1 (HIV-1) infection. HIV-1 derived lentiviral vectors (LVs) transduce DCs at high efficiency but their effects on DC functions have not been carefully studied. Modification of DCs using LVs may lead to important applications in transplantation, treatment of cancer, autoimmune and infectious diseases.


RESULTS
Using DCs prepared from multiple blood donors, we report that LV transduction of DCs resulted in altered DC phenotypes and functions. Lentiviral transduction of DCs resulted in down-regulation of cell surface molecules including CD1a, co-stimulatory molecules CD80, CD86, ICAM-1, and DC-SIGN. DCs transduced with LVs displayed a diminished capacity to polarize naive T cells to differentiate into Th1 effectors. This impaired Th1 response could be fully corrected by co-transduction of DCs with LVs encoding interleukin-12 (IL-12), interferon-gamma (IFN-gamma), or small interfering RNA (siRNA) targeting IL-10.


CONCLUSIONS
DCs transduced with LVs in vitro displayed diminished Th1 functions due to altered DC phenotypes. Our study addresses an important issue concerning lentiviral infection and modification of DC functions, and provides a rational approach using LVs for immunotherapy.
Chen
Xiaochuan
X
Department of Molecular Genetics and Microbiology, Powell Gene Therapy Center, McKnight Brain Institute, University of Florida College of Medicine Gainesville, FL 32610-0266, USA. xchen@ufl.edu
He
Jin
J
Chang
Lung-Ji
LJ
D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D005434:Flow Cytometry; D005822:Genetic Vectors; D006801:Humans; D007111:Immunity, Cellular; D016086:Lentivirus / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014161:Transduction, Genetic
D017931:DNA Primers