Matis L A, Ruscetti S K, Longo D L, Jacobson S, Brown E J, Zinn S, Kruisbeek A M
J Immunol. 1985 Jul;135(1):703-13.
After immunization of B6 mice with the syngeneic retrovirus-induced T cell leukemia/lymphoma FBL-3, two major tumor-specific proliferative T cell clonotypes were derived. T cell clones derived from long-term lines propagated by in vitro culture with irradiated tumor cells and syngeneic spleen cells were exclusively of the Lyt-2+ phenotype. Such clones were cytolytic, retained their proliferative phenotype indefinitely when expanded by repeated cycles of reactivation and rest, and recognized a tumor-specific cell surface antigen in association with class I MHC molecules. This tumor cell antigen was not present on nontransformed virus-infected cells. Class II MHC-restricted MT4+ clones specific for the viral antigen gp70 were derived from lymph node T cells of FBL-3 tumor-immune mice only by in vitro culture with purified Friend virus in the presence of syngeneic splenic APC. Once derived, however, such clones could be stimulated in the presence of FBL-3 tumor cells and syngeneic spleen cells, demonstrating the reprocessing of tumor-derived gp70 antigen by APC in the spleen cell population. In contrast, no reprocessing of the tumor cell surface antigen by splenic APC for presentation to the class I MHC-restricted T cell clones could be demonstrated. Evidence is presented that FBL-3 T leukemia/lymphoma cells function as APC for Lyt-2+ class I MHC-restricted clones, and that no concomitant recognition of Ia molecules is required to activate these clones. Both Lyt-2+ and MT4+ clones were induced to proliferate in the presence of exogenous IL2 alone, but this stimulus failed to result in significant release of immune interferon. In contrast, antigen stimulation of both clones resulted in proliferation as well as significant immune interferon release. Immune interferon production is not required for the generation of MHC-restricted cell-mediated cytolytic function.
用同基因逆转录病毒诱导的T细胞白血病/淋巴瘤FBL-3免疫B6小鼠后，获得了两种主要的肿瘤特异性增殖性T细胞克隆型。通过与经照射的肿瘤细胞和同基因脾细胞进行体外培养而从长期细胞系中获得的T细胞克隆均为Lyt-2+表型。此类克隆具有细胞毒性，在通过反复激活和休息的循环进行扩增时能无限期保留其增殖表型，并识别与I类MHC分子相关的肿瘤特异性细胞表面抗原。这种肿瘤细胞抗原在未转化的病毒感染细胞上不存在。仅通过在同基因脾细胞抗原呈递细胞（APC）存在的情况下与纯化的Friend病毒进行体外培养，从FBL-3肿瘤免疫小鼠的淋巴结T细胞中获得了对病毒抗原gp70具有特异性的II类MHC限制性MT4+克隆。然而，一旦获得此类克隆，在FBL-3肿瘤细胞和同基因脾细胞存在的情况下即可被刺激，这表明脾细胞群体中的APC对肿瘤来源的gp70抗原进行了再加工处理。相比之下，未证明脾细胞APC对肿瘤细胞表面抗原进行再加工处理以呈递给I类MHC限制性T细胞克隆。有证据表明，FBL-3 T白血病/淋巴瘤细胞作为I类MHC限制性Lyt-2+克隆的APC发挥作用，并且激活这些克隆不需要同时识别Ia分子。单独在存在外源性白细胞介素-2（IL2）的情况下，Lyt-2+和MT4+克隆均被诱导增殖，但这种刺激未能导致免疫干扰素的显著释放。相比之下，两种克隆的抗原刺激均导致增殖以及免疫干扰素的显著释放。MHC限制性细胞介导的细胞溶解功能的产生不需要免疫干扰素的产生。
