FBL-reactive CD8+ cytotoxic and CD4+ helper T lymphocytes recognize distinct Friend murine leukemia virus-encoded antigens.
FBL-reactive CD8+ cytotoxic and CD4+ helper T lymphocytes recognize distinct Friend murine leukemia virus-encoded antigens.
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DOI：
10.1084/jem.169.2.457
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发表时间：
1989-02-01
期刊：
影响因子：
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通讯作者：
Greenberg PD
中科院分区：
文献类型：
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作者：
Klarnet JP;Kern DE;Okuno K;Holt C;Lilly F;Greenberg PD
用Friend鼠白血病病毒（F-MuLV）FBL免疫C57 BL/6（B6）小鼠，诱导肿瘤特异性细胞溶解性CD 8+（CTL）和产生淋巴因子的CD 4 + Th，这在携带播散性FBL白血病的B6小鼠的过继治疗中是有效的。本研究评价了FBL上表达的F-MuLV抗原决定簇，这些抗原决定簇被FBL反应性CD 8+和CD 4 + T细胞识别。为了鉴定FBL反应性CD 8 + CTL的特异性，使用了用编码F-MuLV gag或包膜（env）基因产物加上I类限制性元件Db的质粒转染的Fisher大鼠胚胎成纤维细胞（FRE）。FBL反应性CTL识别用F-MuLV gag编码的基因产物转染的FRE靶细胞，但不能识别表达F-MuLV env的靶细胞。尝试通过用含有插入的F-MuLV env基因的重组牛痘病毒免疫产生env特异性CD 8 + CTL是不成功的，尽管产生对牛痘抗原表位的细胞溶解应答，这意味着B6小鼠不能产生针对env决定簇的CD 8 + CTL。相比之下，CD 4 + Th克隆识别用env而不是gag基因转染的FRE靶细胞，并且用重组牛痘病毒免疫诱导env特异性CD 4 + T细胞应答。这些数据表明，在Friend逆转录病毒诱导的肿瘤模型中，肿瘤排斥反应可以由CTL或Th介导，来源于离散逆转录病毒蛋白的抗原主要负责激活每个T细胞亚群。
Immunization of C57BL/6 (B6) mice with FBL, a Friend murine leukemia virus (F-MuLV), induces both tumor-specific cytolytic CD8+ (CTL) and lymphokine-producing CD4+ Th that are effective in adoptive therapy of B6 mice bearing disseminated FBL leukemia. The current study evaluated the F-MuLV antigenic determinants expressed on FBL that are recognized by FBL-reactive CD8+ and CD4+ T cells. To identify the specificity of the FBL-reactive CD8+ CTL, Fisher rat embryo fibroblast (FRE) cells transfected with plasmids encoding F-MuLV gag or envelope (env) gene products plus the class I-restricting element Db were utilized. FBL- reactive CTL recognized FRE target cells transfected with the F-MuLV gag-encoded gene products, but failed to recognize targets expressing F- MuLV env. Attempts to generate env-specific CD8+ CTL by immunization with a recombinant vaccinia virus containing an inserted F-MuLV env gene were unsuccessful, despite the generation of a cytolytic response to vaccinia epitopes, implying that B6 mice fail to generate CD8+ CTL to env determinants. By contrast, CD4+ Th clones recognized FRE target cells transfected with env and not gag genes, and immunization with the recombinant vaccinia virus induced an env-specific CD4+ T cell response. These data show that in a Friend retrovirus-induced tumor model in which tumor rejection can be mediated by either CTL or Th, antigens derived from discrete retroviral proteins are predominantly responsible for activation of each T cell subset.