Flynn J Norman, Pistello Mauro, Isola Patrizia, Zaccaro Lucia, Del Santo Barbara, Ricci Enrica, Matteucci Donatella, Bendinelli Mauro
Dipartimento di Patologia Sperimentale, Università di Pisa, Via San Zeno 37, I-56127 Pisa, Italy.
Clin Diagn Lab Immunol. 2005 Jun;12(6):736-45. doi: 10.1128/CDLI.12.6.736-745.2005.
The potential of immunotherapy with autologous virus-specific T cells to affect the course of feline immunodeficiency virus (FIV) infection was explored in a group of specific-pathogen-free cats infected with FIV a minimum of 10 months earlier. Popliteal lymph node cells were stimulated by cocultivation with UV-inactivated autologous fibroblasts infected with recombinant vaccinia viruses expressing either FIV gag or env gene products, followed by expansion in interleukin-2. One or two infusions of both Gag- and Env-stimulated cells resulted in a slow increase in FIV-specific gamma interferon-secreting T cells in the circulation of cats. In the same animals, viral set points fluctuated widely during the first 2 to 3 weeks after adoptive transfer and then returned to pretreatment levels. The preexisting viral quasispecies was also found to be modulated, whereas no novel viral variants were detected. Circulating CD4(+) counts underwent a dramatic decline early after treatment. CD4/CD8 ratios remained instead essentially unchanged and eventually improved in some animals. In contrast, a single infusion of Gag-stimulated cells alone produced no apparent modulations of infection.
在一组至少于10个月前感染猫免疫缺陷病毒(FIV)的无特定病原体猫中,探索了用自体病毒特异性T细胞进行免疫治疗对FIV感染进程的影响。通过与感染表达FIV gag或env基因产物的重组痘苗病毒的紫外线灭活自体成纤维细胞共培养来刺激腘淋巴结细胞,然后在白细胞介素-2中进行扩增。对Gag刺激细胞和Env刺激细胞进行一到两次输注,导致猫循环中FIV特异性γ干扰素分泌T细胞缓慢增加。在同一批动物中,病毒载量在过继转移后的前2至3周内波动很大,然后恢复到预处理水平。还发现先前存在的病毒准种受到调节,而未检测到新的病毒变体。治疗后早期循环CD4(+)计数急剧下降。相反,CD4/CD8比值基本保持不变,最终在一些动物中有所改善。相比之下,单独单次输注Gag刺激细胞对感染没有明显的调节作用。