The antiviral activity of HIV-specific CD8+ CTL clones is limited by elimination due to encounter with HIV-infected targets.

摘要: Adoptive immunotherapy of virus infection with viral-specific CTL has shown promise in animal models and human infections is being evaluated as a therapy for established HIV-1 infection. Defining the individual obstacles success difficult trials. We have therefore examined localization, persistence, antiviral activity gag-specific clones both HIV-1-infected uninfected haplotype-matched (hu)-PBL-SCID mice. Injection but not control into hosts reduced plasma viremia by >10-fold failed to eliminate from most treated animals. The failure eradicate did reflect selection escape variants because gag epitope remained unmutated isolates obtained after therapy. carboxyfluorescein diacetate succinimide ester-labeled demonstrated markedly different fates presence or absence HIV-1-specific rapidly disappeared infected recipients, whereas they were maintained at high numbers By contrast, long lived recipients. Thus, interaction virus-infected target cells vivo leads only destruction also rapid disappearance infused CTL, it limits capacity