PMID- 9691204 OWN - NLM STAT- MEDLINE DCOM- 19980908 LR - 20180213 IS - 0254-9670 (Print) IS - 0254-9670 (Linking) VI - 15 IP - 2 DP - 1998 TI - In vivo and in vitro modulation of immune stimulatory capacity of primary dendritic cells by adenovirus-mediated gene transduction. PG - 100-11 AB - Dendritic cells (DCs) are potent antigen-presenting cells which are key leukocytes in the initiation of cell-mediated organ graft rejection, antiviral immunity, and antitumor responses. In this study we demonstrate that genetic modification of primary human and mouse DCs by adenoviral gene transfer is an effective means of induction and modulation of antigen presentation by DCs. An adenovirus vector (AdLacZ) was used to express an intracellular model antigen beta-galactosidase (beta-gal) in DCs. Our results show that 30-40% of precursor dendritic cells (PDCs) derived from human umbilical cord blood and circulating mature blood DCs express high levels beta-galactosidase (beta-gal) after infection with AdLacZ with no cytopathic effect observed. In vitro, AdLacZ transduced PDCs and DCs demonstrated a 10- to 20-fold higher mixed lymphocyte reaction (MLR) stimulatory capacity as compared to that of monocytes. In vivo, immunization with AdLacZ transduced mouse DCs resulted in more potent cytotoxic T lymphocyte (CTL) responses against the predicted H-2 restricted beta-gal epitope as compared to CTL responses obtained by beta-gal peptide pulsed DCs. Modulations of the MLR stimulatory capacity of DCs were examined by expression of mouse B7 and CTLA-4Ig. The results show that expression of mouse B7 by a recombinant adenoviral vector (Ad7) significantly enhances the MLR stimulatory capacity of human DCs. In contrast, expression of CTLA-4Ig (AdCTLA-4Ig) reduces the MLR stimulatory capacity of the transduced cells. We conclude that recombinant adenovirus can readily be used for genetic modulation DC-induced immune responses in vivo and in vitro. DCs targeted for induction of specific antigen responses or for modulation of the immune stimulatory capacity may have a potential use in the control of transplantation rejection or viral infections. FAU - Sonderbye, L AU - Sonderbye L AD - Division of Nephrology, Milton S. Hershey Medical Center, Penn State University, Hershey, PA 17033, USA. FAU - Feng, S AU - Feng S FAU - Yacoubian, S AU - Yacoubian S FAU - Buehler, H AU - Buehler H FAU - Ahsan, N AU - Ahsan N FAU - Mulligan, R AU - Mulligan R FAU - Langhoff, E AU - Langhoff E LA - eng GR - AI28734/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - Switzerland TA - Exp Clin Immunogenet JT - Experimental and clinical immunogenetics JID - 8411714 RN - 0 (DNA Primers) SB - IM MH - Adenoviridae/*genetics MH - Animals MH - Antigen Presentation/genetics MH - Base Sequence MH - DNA Primers/genetics MH - Dendritic Cells/*immunology MH - Gene Expression MH - Gene Transfer Techniques MH - Genetic Engineering MH - Genetic Vectors MH - Humans MH - In Vitro Techniques MH - Lac Operon MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - T-Lymphocytes, Cytotoxic/immunology MH - *Transduction, Genetic EDAT- 1998/08/06 02:01 MHDA- 2000/08/16 11:00 CRDT- 1998/08/06 02:01 PHST- 1998/08/06 02:01 [pubmed] PHST- 2000/08/16 11:00 [medline] PHST- 1998/08/06 02:01 [entrez] AID - eci15100 [pii] AID - 10.1159/000019060 [doi] PST - ppublish SO - Exp Clin Immunogenet. 1998;15(2):100-11. doi: 10.1159/000019060.