Actor J K, Shirai M, Kullberg M C, Buller R M, Sher A, Berzofsky J A
Laboratory of Parasitic Disease, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):948-52. doi: 10.1073/pnas.90.3.948.
During the time of egg deposition, schistosome-infected mice exhibit a downregulation in interleukin 2 and interferon gamma production toward parasite antigens, mitogens, and foreign nonparasite protein antigens. To determine whether this imbalance in cytokine response would impact on CD8+ cytotoxic T-lymphocyte (CTL) responses, as well as on immune clearance of viral infections, we challenged Schistosoma mansoni-infected BALB/c mice, when cytokine imbalance was prominent, with a recombinant vaccinia virus expressing human immunodeficiency virus type 1 gp160. In contrast to control vaccinia-infected animals, S. mansoni plus vaccinia-infected mice did not produce significant Th1 cytokine responses upon in vitro stimulation with recombinant gp120, consistent with previous results for nonparasite antigens. However, more striking was the downregulation of the virus-specific CTL response not previously studied. Spleen cells from vaccinia-infected control mice displayed strong CD8+ cytolytic activity against gp160-transfected fibroblasts and fibroblasts pulsed with a peptide (P18) representing a CTL epitope of gp160. In contrast, mice coinfected with S. mansoni and vaccinia manifested absent or markedly reduced in vitro CTL activity even in the presence of exogenous interleukin 2. To determine whether this immune dysregulation might impact on viral clearance, we measured virus titers in tissues as a function of time. Mice infected with vaccinia virus alone rapidly cleared the virus, whereas in animals coinfected with S. mansoni, viral clearance was delayed by as much as 3 weeks in the liver and by several days in the spleen and lungs. These observations suggest that helminth infection may influence immune responses to concurrent viral infections.
在虫卵沉积期间，感染血吸虫的小鼠对寄生虫抗原、丝裂原和外源非寄生虫蛋白抗原的白细胞介素2和干扰素γ产生呈现下调。为了确定这种细胞因子反应的失衡是否会影响CD8 +细胞毒性T淋巴细胞（CTL）反应以及病毒感染的免疫清除，我们在细胞因子失衡显著时，用表达人免疫缺陷病毒1型gp160的重组痘苗病毒攻击曼氏血吸虫感染的BALB / c小鼠。与感染痘苗病毒的对照动物相比，曼氏血吸虫加痘苗病毒感染的小鼠在体外用重组gp120刺激时未产生显著的Th1细胞因子反应，这与先前针对非寄生虫抗原的结果一致。然而，更引人注目的是病毒特异性CTL反应的下调，这是以前未研究过的。来自感染痘苗病毒的对照小鼠的脾细胞对gp160转染的成纤维细胞和用代表gp160的CTL表位的肽（P18）脉冲处理的成纤维细胞表现出强烈的CD8 +溶细胞活性。相比之下，同时感染曼氏血吸虫和痘苗病毒的小鼠即使在存在外源性白细胞介素2的情况下，体外CTL活性也不存在或明显降低。为了确定这种免疫失调是否可能影响病毒清除，我们测量了组织中的病毒滴度随时间的变化。单独感染痘苗病毒的小鼠迅速清除病毒，而在同时感染曼氏血吸虫的动物中，肝脏中的病毒清除延迟多达3周，脾脏和肺部中的病毒清除延迟数天。这些观察结果表明，蠕虫感染可能会影响对同时发生的病毒感染的免疫反应。
