de Vos van Steenwijk Peggy J, Piersma Sytse J, Welters Marij J P, van der Hulst Jeanette M, Fleuren Gertjan, Hellebrekers Bart W J, Kenter Gemma G, van der Burg Sjoerd H
Department of Gynaecology, Leiden University Medical Centre, Leiden, The Netherlands.
Clin Cancer Res. 2008 Nov 15;14(22):7188-95. doi: 10.1158/1078-0432.CCR-08-0994.
To characterize HPV16 E6- and E7-specific T-cell immunity in patients with high-grade squamous intraepithelial lesions (HSIL).
Peripheral blood mononuclear cells isolated from 38 patients with HPV16+ HSIL were used to determine the magnitude, breadth, and polarization of HPV16-specific T-cell responses by proliferation assays and cytokine assays. Furthermore, HSIL-infiltrating T cells isolated from 7 cases were analyzed for the presence of HPV16 E6- and/or E7-specific T cells, phenotyped, and tested for the specific production of IFN-gamma and interleukin-10 as well as for their capacity to suppress immune responses.
HPV16-specific T-cell responses were absent in the circulation of the majority (approximately 60%) of patients who visit the clinic for treatment of a HPV16+ HSIL lesion. Notably, HPV16-specific T-cell reactivity was predominantly detected in patients returning to the clinic for repetitive treatment of a persistent or recurrent HPV16+ HSIL lesion after initial destructive treatment. The majority (> 70%) of these HPV16-specific T-cell responses did not secrete proinflammatory cytokines, indicating that most of the subjects, although in principle able to mount a HPV16-specific immune response, fail to develop protective cellular immunity. This notion is sustained by our observation that only three HSIL-infiltrating T-cell cultures contained HPV16-specific T cells, one of which clearly consisted of HPV16 E7-specific regulatory T cells.
The presence of HPV16-specific T cells with a non-Th1/Th2 cytokine and even suppressive signature in patients with HSIL may affect the outcome of vaccine approaches aiming at reinforcing human papillomavirus-specific immunity to attack human papillomavirus-induced lesions.
对高级别鳞状上皮内病变（HSIL）患者的人乳头瘤病毒16型（HPV16）E6和E7特异性T细胞免疫进行特征分析。
从38例HPV16阳性HSIL患者中分离外周血单个核细胞，通过增殖试验和细胞因子试验确定HPV16特异性T细胞反应的强度、广度和极化情况。此外，对从7例患者中分离的HSIL浸润性T细胞进行分析，检测HPV16 E6和/或E7特异性T细胞的存在情况，进行表型分析，并检测其干扰素-γ和白细胞介素-10的特异性产生情况以及抑制免疫反应的能力。
在因HPV16阳性HSIL病变前来就诊的大多数患者（约60%）的循环系统中，未检测到HPV16特异性T细胞反应。值得注意的是，在初次破坏性治疗后因持续性或复发性HPV16阳性HSIL病变再次前来就诊的患者中，主要检测到了HPV16特异性T细胞反应。这些HPV16特异性T细胞反应中的大多数（>70%）不分泌促炎细胞因子，这表明大多数受试者虽然原则上能够产生HPV16特异性免疫反应，但未能形成保护性细胞免疫。我们的观察结果支持了这一观点，即只有三个HSIL浸润性T细胞培养物中含有HPV16特异性T细胞，其中一个明显由HPV16 E7特异性调节性T细胞组成。
HSIL患者中存在具有非Th1/Th2细胞因子特征甚至具有抑制特征的HPV16特异性T细胞，可能会影响旨在增强人乳头瘤病毒特异性免疫以攻击人乳头瘤病毒诱导病变的疫苗方法的效果。
