PMID- 15518595 OWN - NLM STAT- MEDLINE DCOM- 20060731 LR - 20181113 IS - 1742-4690 (Electronic) IS - 1742-4690 (Linking) VI - 1 DP - 2004 Nov 1 TI - Alteration of T cell immunity by lentiviral transduction of human monocyte-derived dendritic cells. PG - 37 AB - 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. FAU - Chen, Xiaochuan AU - Chen X AD - 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 FAU - He, Jin AU - He J FAU - Chang, Lung-Ji AU - Chang LJ LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. DEP - 20041101 PL - England TA - Retrovirology JT - Retrovirology JID - 101216893 RN - 0 (DNA Primers) SB - IM MH - Base Sequence MH - CD4-Positive T-Lymphocytes/cytology/immunology MH - DNA Primers MH - Dendritic Cells/immunology/*virology MH - Flow Cytometry MH - Genetic Vectors MH - Humans MH - *Immunity, Cellular MH - Lentivirus/genetics/*immunology MH - Molecular Sequence Data MH - Monocytes/immunology/virology MH - T-Lymphocytes/*immunology/virology MH - Transduction, Genetic PMC - PMC534092 EDAT- 2004/11/03 09:00 MHDA- 2006/08/01 09:00 PMCR- 2004/11/01 CRDT- 2004/11/03 09:00 PHST- 2004/06/28 00:00 [received] PHST- 2004/11/01 00:00 [accepted] PHST- 2004/11/03 09:00 [pubmed] PHST- 2006/08/01 09:00 [medline] PHST- 2004/11/03 09:00 [entrez] PHST- 2004/11/01 00:00 [pmc-release] AID - 1742-4690-1-37 [pii] AID - 10.1186/1742-4690-1-37 [doi] PST - epublish SO - Retrovirology. 2004 Nov 1;1:37. doi: 10.1186/1742-4690-1-37.