Gamadia L E, Rentenaar R J, Baars P A, Remmerswaal E B, Surachno S, Weel J F, Toebes M, Schumacher T N, ten Berge I J, van Lier R A
Renal Transplant Unit, Department of Internal Medicine, Academic Medical Center, The Netherlands Cancer Institute, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Blood. 2001 Aug 1;98(3):754-61. doi: 10.1182/blood.v98.3.754.
During immunosuppression, cytomegalovirus (CMV) can reactivate and cause serious clinical problems. Normally, abundant virus replication is suppressed by immune effector mechanisms. To study the interaction between CD8(+) T cells and persisting viruses, frequencies and phenotypes of CMV-specific CD8(+) T cells were determined in healthy individuals and compared to those in renal transplant recipients. In healthy donors, function of circulating virus-specific CD8(+) T cells, as measured by peptide-induced interferon gamma (IFN-gamma) production, but not the number of virus-specific T cells enumerated by binding of specific tetrameric peptide/HLA complexes, correlated with the number of CMV-specific IFN-gamma-secreting CD4(+) helper T cells. Circulating CMV- specific CD8(+) T cells did not express CCR7 and may therefore not be able to recirculate through peripheral lymph nodes. Based on coexpression of CD27 and CD45R0 most CMV-specific T cells in healthy donors appeared to be memory-type cells. Remarkably, frequencies of CMV-specific CD8(+) T cells were significantly higher in immunosuppressed individuals than in healthy donors. In these patients CMV-specific cells predominantly had an effector phenotype, that is, CD45R0(+)CD27(-)CCR7(-) or CD45RA(+)CD27(-)CCR7(-) and contained both granzyme B and perforin. Our data show that in response to immunosuppressive medication quantitative and qualitative changes occur in the CD8(+) T-cell compartment. These adaptations may be instrumental to maintain CMV latency. (Blood. 2001;98:754-761)
在免疫抑制期间，巨细胞病毒（CMV）可重新激活并引发严重的临床问题。正常情况下，丰富的病毒复制会被免疫效应机制所抑制。为了研究CD8(+) T细胞与持续存在的病毒之间的相互作用，我们测定了健康个体中CMV特异性CD8(+) T细胞的频率和表型，并将其与肾移植受者的进行比较。在健康供者中，通过肽诱导的干扰素γ（IFN-γ）产生来衡量的循环病毒特异性CD8(+) T细胞的功能，而非通过特异性四聚体肽/HLA复合物结合所列举的病毒特异性T细胞数量，与CMV特异性IFN-γ分泌性CD4(+)辅助性T细胞的数量相关。循环中的CMV特异性CD8(+) T细胞不表达CCR7，因此可能无法通过外周淋巴结再循环。基于CD27和CD45R0的共表达，健康供者中大多数CMV特异性T细胞似乎是记忆型细胞。值得注意的是，免疫抑制个体中CMV特异性CD8(+) T细胞的频率显著高于健康供者。在这些患者中，CMV特异性细胞主要具有效应器表型，即CD45R0(+)CD27(-)CCR7(-)或CD45RA(+)CD27(-)CCR^{7(-)}，并且同时含有颗粒酶B和穿孔素。我们的数据表明，响应免疫抑制药物，CD8(+) T细胞区室会发生数量和质量上的变化。这些适应性变化可能有助于维持CMV潜伏状态。（《血液》。2001年；98:754 - 761）
