Sester Martina, Sester Urban, Gärtner Barbara C, Girndt Matthias, Meyerhans Andreas, Köhler Hans
Medical Department IV, Division of Nephrology, University of the Saarland, Homburg, Germany.
J Am Soc Nephrol. 2002 Oct;13(10):2577-84. doi: 10.1097/01.asn.0000030141.41726.52.
Cellular immune responses are of high importance in initiating and maintaining immunity against virus infections. Whereas the cellular immune response during persistent cytomegalovirus (CMV) infection is well assessable, the individual contribution of CD4 and CD8 T cell responses during primary infection has not been described. A novel whole-blood assay, which relies on the flow-cytometric detection of antigen-induced cytokine expression, was used to characterize CMV-specific CD4 and CD8 T cell responses during primary infection of CMV seronegative recipients of a renal allograft from a CMV seropositive donor. These T cell responses were compared with long-term CMV-positive patients with known history of transplantation-related seroconversion. Results were further correlated to CMV load and serum IgG and IgM. The long-term seroconverted patients consistently showed a dominant CMV-specific CD4 T cell response (median frequencies: CD4, 1.12% [range, 0.35 to 8.10%] versus CD8 0.13% [range, <0.05 to 0.55%]). In contrast, during primary infection, the cellular immune response is strongly dominated by CMV-specific CD8 T cells (median peak frequencies: CD4, 1.24% [range, 0.21 to 1.60%] versus CD8, 2.47% [range, 1.34 to 6.67%]). Upon receipt of ganciclovir, viral load as well as CMV-specific CD8 responses decreased. The frequency of the respective CD4 T cells fluctuated during decrease of CMV load and became dominant over CMV-specific CD8 T cell responses. These results are consistent with the view of an effective direct antiviral activity of CD8 T cells, which is most critical during periods of high viremia. Later on during persistent infection, CD4 T cells dominate the immune response to support the state of antiviral immunity.
细胞免疫反应在启动和维持针对病毒感染的免疫中具有高度重要性。虽然持续性巨细胞病毒（CMV）感染期间的细胞免疫反应易于评估，但原发性感染期间CD4和CD8 T细胞反应的个体贡献尚未得到描述。一种新型全血检测方法，该方法依赖于对抗原诱导的细胞因子表达进行流式细胞术检测，用于表征来自CMV血清阳性供体的肾移植CMV血清阴性受者原发性感染期间的CMV特异性CD4和CD8 T细胞反应。将这些T细胞反应与有移植相关血清转化已知病史的长期CMV阳性患者进行比较。结果进一步与CMV载量以及血清IgG和IgM相关。长期血清转化患者始终表现出占主导地位的CMV特异性CD4 T细胞反应（中位频率：CD4，1.12%[范围，0.35%至8.10%]对CD8 0.13%[范围，<0.05%至0.55%]）。相比之下，在原发性感染期间，细胞免疫反应强烈地由CMV特异性CD8 T细胞主导（中位峰值频率：CD4，1.24%[范围，0.21%至1.60%]对CD8，2.47%[范围，1.34%至6.67%]）。接受更昔洛韦后，病毒载量以及CMV特异性CD8反应降低。在CMV载量下降期间，相应CD4 T细胞的频率波动，并超过CMV特异性CD8 T细胞反应而占主导地位。这些结果与CD8 T细胞具有有效的直接抗病毒活性的观点一致，这在高病毒血症期间最为关键。在持续性感染后期，CD4 T细胞主导免疫反应以维持抗病毒免疫状态。
