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• W1568334393 endingPage "5139" @default.
• W1568334393 startingPage "5132" @default.
• W1568334393 abstract "We have used delayed-type hypersensitivity (DTH) responses to probe the mechanisms of drug-induced cardiac allograft acceptance in mice. DBA/2-->C57BL/6 cardiac allograft recipients treated transiently with gallium nitrate accept their grafts for >90 days and fail to display DBA/2-reactive DTH responses. These DTH responses are restored when anti-TGF-beta Abs are included at the challenge site, and cell depletion studies showed that this DTH inhibition is mediated by CD4+ cells. Real-time PCR analysis revealed that allograft acceptor mice produce no more than background levels of TGF-beta mRNA at DTH challenge sites. This suggests that DTH regulation in allograft acceptor mice may involve TGF-beta activation, rather than TGF-beta production. The protease, plasmin, can activate TGF-beta, and activated T cells can express a receptor for the plasmin-producing enzyme urokinase-type plasminogen activator (uPA), and can also produce both uPA and tissue-type plasminogen activator (tPA). We observed that Abs to tPA or uPA can replace anti-TGF-beta mAb for the restoration of donor-reactive DTH responses in allograft acceptor mice. Histologic analysis revealed that accepted cardiac allografts express uPA, tPA, and active TGF-beta, whereas accepted cardiac isografts express only tPA, but not uPA or activated TGF-beta. These data demonstrate that local tPA and uPA contribute to DTH regulation in allograft acceptor mice and suggest that these elements of the fibrinolytic pathway are used to control donor-reactive cell-mediated immunity in allograft acceptor mice." @default.
• W1568334393 created "2016-06-24" @default.
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• W1568334393 date "2000-05-15" @default.
• W1568334393 modified "2023-10-14" @default.
• W1568334393 title "Mechanisms of Graft Acceptance: Evidence That Plasminogen Activator Controls Donor-Reactive Delayed-Type Hypersensitivity Responses in Cardiac Allograft Acceptor Mice" @default.
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• W1568334393 doi "https://doi.org/10.4049/jimmunol.164.10.5132" @default.
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