CD4+ T-cell activation by antigen-presenting cells infected with urease-deficient recombinant Mycobacterium bovis bacillus Calmette-Guérin

Authors


  • Editor: Patrick Brennan

Correspondence: Masahiko Makino, Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama, Tokyo 189-0002, Japan. Tel.: +81 42 391 8059; fax: +81 42 391 8212; e-mail: mmaki@nih.go.jp

Abstract

We constructed a recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG-ΔUT) that lacks urease, providing acidic intraphagosomal conditions to drive an effective human immune T-cell response. BCG-ΔUT-infected macrophages stimulated autologous CD4+ T cells more efficiently than parent BCG-infected macrophages. For further T-cell activation, BCG-ΔUT-infected macrophages required pretreatment with exogenous recombinant granulocyte-macrophage colony-stimulating factor or costimulation with either CD40 ligand or interferon-γ. By contrast, BCG-ΔUT-infected dendritic cells induced significant activation of naïve CD4+ T cells without costimulating signals. C57BL/6 mice intradermally inoculated with BCG-ΔUT more efficiently produced memory T cells that responded to recall antigen. Therefore, the depletion of urease from BCG is useful for the activation of T cells.

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