Marzo A L, Lake R A, Robinson B W, Scott B
University Department of Medicine, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia.
Cancer Res. 1999 Mar 1;59(5):1071-9.
The role of tumor-specific CD8 and CD4 lymphocytes in rejecting solid tumors has been difficult to determine because of the lack of models in which tumor antigen, specific CD8 cells, and specific CD4 cells can be monitored and controlled. To investigate the minimal components required for the induction and maintenance of CTL activity sufficient to reject a solid tumor in vivo, we transfected the influenza hemagglutinin (HA) gene into a nonimmunogenic class I+/class II- murine malignant mesothelioma (MM) tumor line to generate an endogenous tumor antigen and used TCR transgenic mice with class I- or class II-restricted specificities for HA as sources of naive, tumor-specific T cells. The data show that the presence of a strong tumor antigen is not in itself sufficient to induce an effective CTL response, nor does the presence of a high frequency of precursor cells guarantee tumor rejection. We also show that tumor-specific CD4 cells, when CTL numbers are suboptimal, greatly enhance the eradication of tumor, confirming the importance of antigen-presenting cell presentation of tumor antigens to class II-restricted cells. These data confirm that T-cell receptor transgenic cells, combined with nominal tumor antigen transfection, represent powerful tools to analyze tumor-specific T-cell responses.
由于缺乏能够监测和控制肿瘤抗原、特异性CD8细胞及特异性CD4细胞的模型，肿瘤特异性CD8和CD4淋巴细胞在实体瘤排斥反应中的作用一直难以确定。为了研究在体内诱导和维持足以排斥实体瘤的CTL活性所需的最少成分，我们将流感血凝素（HA）基因转染到一个无免疫原性的I类+/II类-小鼠恶性间皮瘤（MM）肿瘤系中，以产生内源性肿瘤抗原，并使用对HA具有I类或II类限制性特异性的TCR转基因小鼠作为初始肿瘤特异性T细胞的来源。数据表明，强肿瘤抗原的存在本身并不足以诱导有效的CTL反应，前体细胞的高频率存在也不能保证肿瘤被排斥。我们还表明，当CTL数量未达最佳时，肿瘤特异性CD4细胞能极大地增强肿瘤的根除，证实了抗原呈递细胞将肿瘤抗原呈递给II类限制性细胞的重要性。这些数据证实，T细胞受体转基因细胞与名义上的肿瘤抗原转染相结合，是分析肿瘤特异性T细胞反应的有力工具。
