Department of Dermatology, University Hospital of Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
Innate Immunity, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
J Dermatol Sci. 2015 Jan;77(1):37-45. doi: 10.1016/j.jdermsci.2014.11.002. Epub 2014 Nov 18.
Infection with different species of cutaneous human papillomaviruses (cHPV) of genus alpha (cαHPVs) and associated skin disease are highly prevalent in solid organ transplant recipients (OTR), documenting the importance of the immunological control of HPV infection.
To investigate the natural course of cαHPV-specific cellular and humoral immune responses during systemic long-term immunosuppression.
Integrating bead-based multiplex serology and flow cytometry we analyzed natural cαHPV-specific antibodies and T(H) cell responses against the major capsid protein L1 of HPV types 2, 27, 57 (species 4) and 3, 10 and 77 (species 2) in sera and blood of OTR before and after initiation of iatrogenic immunosuppression and in comparison to immunocompetent individuals (IC).
Among OTR we observed an overall 42% decrease in humoral L1-specific immune responses during the course of iatrogenic immunosuppression, comparing median values 30 d before and 30 d after initiation of immunosuppressive therapy (p < 0.05). This difference disappeared after long-term (>1 year) immunosuppression. The predominant cellular L1-specific immune response was of type T(H)1 (CD4(+)CD40L(+)IL-2(+)IFN-γ(+)). Consistent with the detected L1-specific antibody titers, L1-specific T(H)1 responses were unchanged in long-term immunosuppressed OTR compared to IC. Notably, cαHPV-L1-specific IL-2(+)/CD40L(+)CD4(+) or IFN-γ(+)/CD40L(+) CD4(+) T(H) cell responses against any of the cαHPV-L1 types were significantly higher in OTR with clinically apparent common warts.
The systemic humoral immune response against cαHPV may reflect the individual degree of iatrogenic immunosuppression indicating a higher susceptibility for cαHPV infection among OTR during the early phase after organ transplantation. Humoral cαHPV-specific immune responses may show a reconstitution to pre-transplantation levels despite continuous potent immunosuppression.
不同种属的皮肤人乳头瘤病毒（cHPV）感染和相关皮肤疾病在实体器官移植受者（OTR）中非常普遍，这证明了免疫控制 HPV 感染的重要性。
研究系统性长期免疫抑制过程中 cαHPV 特异性细胞和体液免疫反应的自然过程。
我们结合基于珠子的多重血清学和流式细胞术分析了 OTR 血清和血液中针对 HPV 2、27、57（种属 4）和 3、10 和 77（种属 2）主要衣壳蛋白 L1 的天然 cαHPV 特异性抗体和 T（H）细胞反应，在开始医源性免疫抑制前后，并与免疫功能正常的个体（IC）进行比较。
在 OTR 中，我们观察到在医源性免疫抑制过程中，体液 L1 特异性免疫反应总体下降了 42%，比较免疫抑制治疗开始前 30 天和开始后 30 天的中位数（p < 0.05）。这种差异在长期（>1 年）免疫抑制后消失。主要的细胞 L1 特异性免疫反应是 T（H）1 型（CD4（+）CD40L（+）IL-2（+）IFN-γ（+））。与检测到的 L1 特异性抗体滴度一致，与 IC 相比，长期免疫抑制的 OTR 中 L1 特异性 T（H）1 反应没有变化。值得注意的是，针对任何 cαHPV-L1 型，cαHPV-L1 特异性 IL-2（+）/CD40L（+）CD4（+）或 IFN-γ（+）/CD40L（+）CD4（+）T（H）细胞反应在临床上明显有寻常疣的 OTR 中均显著更高。
针对 cαHPV 的系统性体液免疫反应可能反映了医源性免疫抑制的个体程度，表明 OTR 在器官移植后早期感染 cαHPV 的易感性更高。尽管持续进行强烈的免疫抑制，体液 cαHPV 特异性免疫反应可能会恢复到移植前的水平。
