Longitudinal analysis of feline leukemia virus-specific cytotoxic T lymphocytes: Correlation with recovery from infection
Longitudinal analysis of feline leukemia virus-specific cytotoxic T lymphocytes: Correlation with recovery from infection
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DOI：
10.1128/jvi.76.5.2306-2315.2002
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发表时间：
2002-03-01
影响因子：
5.4
通讯作者：
Jarrett, O
中科院分区：
文献类型：
--
作者：
Flynn, JN;Dunham, SP;Jarrett, O
猫白血病病毒（FeLV）是一种在家猫中常见的自然发生的伽马病毒，与造血系统的退行性疾病、免疫缺陷和肿瘤有关。虽然暴露于FeLV的大多数猫会发生短暂感染并恢复，但仍有一部分猫会持续病毒血症，许多猫随后会患上致命疾病。为了确定导致感染结果的主要宿主免疫效应机制，我们研究了一组未经治疗的猫在经口接触FeLV后FeLV特异性细胞毒性T淋巴细胞（ctl）的纵向变化。利用Cr-51释放法测量体外病毒特异性细胞毒性，通过检测感染性病毒、FeLV p27衣壳抗原和血液中的原病毒DNA来评估新出现的病毒特异性CTL反应与病毒负荷调节相关。高水平的循环FeLV特异性效应ctl出现在暴露于FeLV后恢复的猫的病毒中和抗体之前。相反，持续性病毒血症与病毒特异性体液和细胞介导的宿主免疫效应机制的沉默有关。2 × 10(7)和1 × 10(8)自体抗原活化淋巴细胞的单次转移与体内病毒负荷下调有关。这些结果表明felv特异性ctl在逆转录病毒免疫中发挥重要作用，并证明了通过抗原特异性T细胞在体内的过继转移来调节疾病结果的潜力。
Feline leukemia virus (FeLV) is a common naturally occurring gammaretrovirus of domestic cats that is associated with degenerative diseases of the hematopoietic system, immunodeficiency, and neoplasia. Although the majority of cats exposed to FeLV develop a transient infection and recover, a proportion of cats become persistently viremic and many subsequently develop fatal diseases. To define the dominant host immune effector mechanisms responsible for the outcome of infection, we studied the longitudinal changes in FeLV-specific cytotoxic T lymphocytes (CTLs) in a group of naive cats following oronasal exposure to FeLV. Using Cr-51 release assays to measure ex vivo virus-specific cytotoxicity, the emerging virus-specific CTL response was correlated with modulations in viral burden as assessed by detection of infectious virus, FeLV p27 capsid antigen, and proviral DNA in the blood. High levels of circulating FeLV-specific effector CTLs appeared before virus neutralizing antibodies in cats that recovered from exposure to FeLV. In contrast, persistent viremia was associated with a silencing of virus-specific humoral and cell-mediated host immune effector mechanisms. A single transfer of between 2 X 10(7) and 1 X 10(8) autologous, antigen-activated lymphoblasts was associated with a downmodulation in viral burden in vivo. The results suggest an important role for FeLV-specific CTLs in retroviral immunity and demonstrate the potential to modulate disease outcome by the adoptive transfer of antigen-specific T cells in vivo.