CD4+ T-cell activation by antigen-presenting cells infected with urease-deficient recombinant Mycobacterium bovis bacillus Calmette-Guérin.
We constructed a recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG-Delta UT) that lacks urease, providing acidic intraphagosomal conditions to drive an effective human immune T-cell response. BCG-Delta UT-infected macrophages stimulated autologous CD4+ T cells more efficiently than parent BCG-infected macrophages. For further T-cell activation, BCG-Delta UT-infected macrophages required pretreatment with exogenous recombinant granulocyte-macrophage colony-stimulating factor or costimulation with either CD40 ligand or interferon-gamma. By contrast, BCG-Delta UT-infected dendritic cells induced significant activation of naïve CD4+ T cells without costimulating signals. C57BL/6 mice intradermally inoculated with BCG-Delta UT 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.
Mukai
Tetsu
T
Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
Maeda
Yumi
Y
Tamura
Toshiki
T
Miyamoto
Yuji
Y
Makino
Masahiko
M
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D008213:Lymphocyte Activation; D008264:Macrophages; D051379:Mice; D008810:Mice, Inbred C57BL; D016254:Mutagenesis, Insertional; D009163:Mycobacterium bovis / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D014510:Urease / Q000172:deficiency* / Q000276:immunology
D004269:DNA, Bacterial; D053583:Interleukin-1beta; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma; D014510:Urease