Open AccessCD4 + T‐cell activation by antigen‐presenting cells infected with urease‐deficient recombinant Mycobacterium bovis bacillus Calmette‐Guérin
Author(s) -
Mukai Tetsu,
Maeda Yumi,
Tamura Toshiki,
Miyamoto Yuji,
Makino Masahiko
Publication year - 2008
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.2008.00407.x
Subject(s) - mycobacterium bovis , microbiology and biotechnology , biology , recombinant dna , t cell , antigen , cd40 , immune system , interferon gamma , mycobacterium , mycobacterium tuberculosis , immunology , bacteria , cytotoxic t cell , tuberculosis , in vitro , medicine , biochemistry , pathology , gene , genetics
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.