Marzo A L, Lake R A, Lo D, Sherman L, McWilliam A, Nelson D, Robinson B W, Scott B
University Department of Medicine, Queen Elizabeth II Medical Center, Nedlands, Western Australia, Australia.
J Immunol. 1999 May 15;162(10):5838-45.
Tumor growth is rarely associated with a strong specific CTL response, suggesting that the immune system is ignorant of the presence of tumor because the Ags are not readily available to or are sequestered from potential effector cells. We studied the in vivo activation of naive TCR transgenic hemagglutinin (HA)-specific CD8+ T cells adoptively transferred into mice bearing HA-expressing tumor using 5,6-carboxy-succinimidyl-fluorescein-ester labeling, which allows the identification of proliferating HA-specific T cells. We demonstrate that tumor Ags are constitutively presented in the lymph nodes draining tumors and are powerfully mitogenic for responding T cells despite the absence of anti-tumor CTL responses. Importantly, this proliferative signal occurs throughout tumor growth and is still detectable 6 mo after tumor inoculation when tumor is not palpable. These results provide the first evidence that there is constitutive presentation of tumor Ags in draining lymph nodes.
肿瘤生长很少与强烈的特异性细胞毒性T淋巴细胞(CTL)反应相关,这表明免疫系统对肿瘤的存在处于无知状态,因为抗原不易被潜在的效应细胞获取或被隔离。我们使用5,6-羧基-琥珀酰亚胺基-荧光素酯标记法研究了过继转移到携带表达血凝素(HA)肿瘤的小鼠体内的初始T细胞受体转基因HA特异性CD8⁺T细胞的体内激活情况,该标记法可用于识别增殖的HA特异性T细胞。我们证明,尽管没有抗肿瘤CTL反应,但肿瘤抗原在引流肿瘤的淋巴结中持续存在,并且对反应性T细胞具有强大的促有丝分裂作用。重要的是,这种增殖信号在肿瘤生长的全过程中都会出现,并且在肿瘤接种6个月后,当肿瘤无法触及时仍可检测到。这些结果首次证明在引流淋巴结中存在肿瘤抗原的持续呈递。