02079nas a2200421   4500000000100000008004100001260001300042653001200055653002500067653003100092653001900123653003800142653001100180653002300191653002200214653002100236653001900257653002200276653002600298653001600324653000900340653002300349653002900372653002400401653002500425653003700450653001100487100001200498700001200510700001300522700001500535700001300550245014500563300001100708490000700719520091700726022001401643       2008                            d  c2008 Jun10aAnimals10aAntigen Presentation10aCD4-Positive T-Lymphocytes10aDNA, Bacterial10aEnzyme-Linked Immunosorbent Assay10aHumans10aImmunologic Memory10aImmunophenotyping10aInterferon-gamma10aInterleukin-1210aInterleukin-1beta10aLymphocyte Activation10aMacrophages10aMice10aMice, Inbred C57BL10aMutagenesis, Insertional10aMycobacterium bovis10aRecombinant Proteins10aSpecific Pathogen-Free Organisms10aUrease1 aMukai T1 aMaeda Y1 aTamura T1 aMiyamoto Y1 aMakino M00aCD4+ T-cell activation by antigen-presenting cells infected with urease-deficient recombinant Mycobacterium bovis bacillus Calmette-Guérin.  a96-1060 v533 a<p>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.</p>  a0928-8244