前沿：CD4 + T细胞对CD8 + T细胞针对模型肿瘤抗原反应性的调控
Cutting edge: CD4+ T cell control of CD8+ T cell reactivity to a model tumor antigen.
作者信息
Surman D R, Dudley M E, Overwijk W W, Restifo N P
机构信息
Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA.
出版信息
J Immunol. 2000 Jan 15;164(2):562-5. doi: 10.4049/jimmunol.164.2.562.
Neoantigens resulting from the inherent genomic instability of tumor cells generally do not trigger immune recognition. Similarly, transfection of tumors with model Ags often fails to elicit CD8+ T cell responses or alter a tumor's growth rate or lethality. We report here that the adoptive transfer of activated Th1-type CD4+ T cells specific for a model tumor Ag results in the de novo generation of CD8+ T cells with specificity to that Ag and concomitant tumor destruction. The anti-tumor effects of the CD4+ T cells required the presence of both MHC class I and class II on host cells, as evidenced by experiments in knockout mice, suggesting that CD4+ T cells enhanced the ability of host APC to activate endogenous CD8+ T cells. These results indicate that the apparent inability of tumor cells expressing highly immunogenic epitopes to activate tumor-specific CD8+ T cells can be altered by activated CD4+ T cells.
肿瘤细胞固有基因组不稳定性产生的新抗原通常不会引发免疫识别。同样，用模型抗原转染肿瘤往往无法引发CD8⁺ T细胞反应，也不会改变肿瘤的生长速度或致死率。我们在此报告，对模型肿瘤抗原具有特异性的活化Th1型CD4⁺ T细胞的过继转移导致了对该抗原有特异性的CD8⁺ T细胞的重新产生以及伴随的肿瘤破坏。CD4⁺ T细胞的抗肿瘤作用需要宿主细胞上同时存在MHC I类和II类分子，基因敲除小鼠实验证明了这一点，这表明CD4⁺ T细胞增强了宿主抗原呈递细胞激活内源性CD8⁺ T细胞的能力。这些结果表明，表达高度免疫原性表位的肿瘤细胞激活肿瘤特异性CD8⁺ T细胞的明显无能可以被活化的CD4⁺ T细胞改变。
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