Lentiviral gp34/OX40L gene transfer into dendritic cells facilitates alloreactive CD4+ T-cell response in vitro.
Gene-modified dendritic cells (DCs) are promising targets for cancer immunotherapy. In this study, we demonstrated that lentiviral transduction of DCs with the gp34/OX40L gene, one of the costimulatory molecules, facilitates alloreactive CD4+ T-cell response in vitro. We achieved a 20% to 40% efficiency of gp34/OX40L gene transfer into DCs by the lentiviral vector, and lentiviral gp34/OX40L gene transfer did not alter the surface phenotype of either immature or mature DCs, suggesting that expression of gp34/OX40L did not induce the maturation of immature DCs and that gp34/OX40L-transduced DCs could fully differentiate into mature DCs. gp34/OX40L gene transfer facilitated an allogeneic CD4+ T-cell response in vitro by mature DCs but not by immature DCs. Dose escalation of the transgene induced an increasing amount of gp34/OX40L expression, leading to an increasing level of up-regulation of the allogeneic CD4+ T-cell response. The addition of anti-gp34 monoclonal antibody totally abrogated this up-regulation. These results suggest that this facilitation of allogeneic CD4+ T-cell response is specifically dependent on gp34/OX40L expressed on transduced DCs. Taken together, our findings show that gp34/ OX40L plays an important role in allogeneic CD4+ T-cell activation by DCs and that lentiviral gp34/OX40L gene transfer into DCs may be a useful strategy for cancer immunotherapy.
Kobayashi
Masayuki
M
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Takaori-Kondo
Akifumi
A
Fukunaga
Keiko
K
Miyoshi
Hiroyuki
H
Uchiyama
Takashi
T
D000954:Antigens, Surface / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D016130:Immunophenotyping; D016086:Lentivirus / Q000235:genetics; D008565:Membrane Proteins; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D014161:Transduction, Genetic / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000494:pharmacology*
D000954:Antigens, Surface; D008565:Membrane Proteins; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; D014409:Tumor Necrosis Factor-alpha