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International Journal of Hematology

, Volume 79, Issue 4, pp 377–383 | Cite as

Lentiviral gp34/OX40L Gene Transfer into Dendritic Cells Facilitates Alloreactive CD4+ T-Cell Response In Vitro

  • Masayuki Kobayashi
  • Akifumi Takaori-Kondo
  • Keiko Fukunaga
  • Hiroyuki Miyoshi
  • Takashi Uchiyamaa
Article

Abstract

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.

Key words

Lentiviral vector OX40/OX40L Gene-modified dendritic cells Allogeneic T-cell response Flow cytometric analysis 

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Copyright information

© The Japanese Society of Hematology 2004

Authors and Affiliations

  • Masayuki Kobayashi
    • 1
  • Akifumi Takaori-Kondo
    • 1
  • Keiko Fukunaga
    • 1
  • Hiroyuki Miyoshi
    • 2
  • Takashi Uchiyamaa
    • 1
  1. 1.Department of Hematology and Oncology, Graduate School of MedicineKyoto UniversityKyotoJapan
  2. 2.Subteam for Manipulation of Cell FateBioResource Center, RIKEN Tsukuba InstituteTsukuba, IbaragiJapan

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