T-cell response to cottontail rabbit papillomavirus structural proteins in infected rabbits.
T-cell response to cottontail rabbit papillomavirus structural proteins in infected rabbits.
复制标题
感染兔子中 T 细胞对棉尾兔乳头瘤病毒结构蛋白的反应。
DOI：
10.1128/jvi.68.6.4043-4048.1994
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发表时间：
1994
影响因子：
5.4
通讯作者：
Wettstein,FO
中科院分区：
文献类型：
--
作者：
Selvakumar,R;Borenstein,LA;Lin,YL;Ahmed,R;Wettstein,FO
棉尾兔乳头瘤病毒（CRPV）诱导的乳头瘤进展为癌的频率很高，因此可以作为高癌症风险的人乳头瘤病毒感染的模型。以前，我们已经表明，非结构和结构蛋白的抗体检测到只有一小部分的乳头状瘤动物。然而，随着乳头状瘤进展为癌，对结构蛋白的抗体应答急剧增加（Y. L.林湖，澳-地A.博伦施泰因河，巴西-地塞尔瓦库马尔河Ahmed和F. O. Wettstein，J. Virol. 67：382-389，1993）。在此，我们监测了在感染过程中，特别是在从乳头状瘤到癌的进展过程中对病毒蛋白的细胞免疫反应。这是通过测量外周血单核细胞（PBMC）对CRPV结构蛋白L1和L2的体外增殖反应来完成的。通过选择性去除B或T细胞将增殖细胞鉴定为T细胞。一般来说，T细胞反应是低的乳头状瘤阶段的兔子，没有响应L2。来自癌症动物的淋巴细胞对L1的反应更频繁，更强烈，超过一半的淋巴细胞对L2也有反应。除了刺激PBMC外，还可以用淋巴结和脾细胞证明L1和L2特异性增殖。总之，我们的数据表明，乳头状瘤发展为癌与CRPV结构蛋白的T细胞应答增加以及体液应答增加有关。然而，这种更大的免疫反应性与结构蛋白的选择性表达增加无关，因为从乳头状瘤和癌中分离的RNA含有类似的晚期和早期RNA的相对水平，如斑点印迹分析所示。因此，在荷瘤兔中观察到的增强的免疫反应性很可能反映了由于肿瘤的扩散而对免疫系统的更大刺激。这些发现表明，乳头状瘤病毒蛋白的免疫反应增加可能是癌进展的预后，特别是转移的发展。
Cottontail rabbit papillomavirus (CRPV)-induced papillomas progress at a high frequency to carcinomas and thus can serve as a model for high-cancer-risk human papillomavirus infection. Previously, we have shown that antibodies to nonstructural and structural proteins are detected in only a fraction of papilloma-bearing animals. However, the antibody response to structural proteins drastically increases as papillomas progress to carcinoma (Y.-L. Lin, L. A. Borenstein, R. Selvakumar, R. Ahmed, and F. O. Wettstein, J. Virol. 67:382-389, 1993). Here we have monitored the cellular immune response to viral proteins during the course of infection and particularly during progression from papilloma to carcinoma. This was done by measuring the in vitro proliferation response of peripheral blood mononuclear cells (PBMCs) to CRPV structural proteins L1 and L2. The proliferating cells were identified as T cells by selective removal of B or T cells. In general, the T-cell response was low for rabbits at the papilloma stage and none responded to L2. Lymphocytes from animals with carcinomas more frequently and more strongly responded to L1, and more than half also responded to L2. In addition to stimulation of PBMCs, L1- and L2-specific proliferation could also be demonstrated with lymph node and spleen cells. Overall, our data show that progression of papilloma to carcinoma is associated with an increased T-cell response to CRPV structural proteins in addition to an increased humoral response. This greater immune reactivity, however, was not associated with a selectively increased expression of structural proteins, since RNA isolated from papillomas and carcinomas contained similar relative levels of late and early RNA as shown by dot blot analysis. Thus, the heightened immune reactivity seen in carcinoma-bearing rabbits most likely reflects greater stimulation of the immune system owing to dissemination of the tumor. These findings suggest that increased immune responses to papillomavirus proteins may be prognostic of progression to carcinoma and particularly of the development of metastases.