Riddell S R, Reusser P, Greenberg P D
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Rev Infect Dis. 1991 Nov-Dec;13 Suppl 11:S966-73. doi: 10.1093/clind/13.supplement_11.s966.
The occurrence of life-threatening infections, including cytomegalovirus (CMV) infection, in recipients of allogeneic bone marrow transplants is related to the severe and prolonged immunodeficiency that is present after transplantation. Studies performed in our laboratory of the recovery of CMV-specific T cell responses after bone marrow transplantation have demonstrated that CMV disease occurs exclusively in those patients with no reconstitution of CD8+ CMV-specific T cell responses. Methods of isolating class I major histocompatibility complex-restricted CD8+ CMV-specific T cell clones from healthy CMV-seropositive individuals with protective immunity have been developed. The majority of cytotoxic T cell clones isolated from several individuals recognize structural proteins of the virion that are presented by infected cells without requiring the expression of the viral gene. These results suggest this immunodominant response may be essential for maintaining the virus in a latent state in healthy CMV-seropositive individuals. Clinical trials have been initiated at our institution to investigate the potential for selective reconstitution of CMV-specific immunity in bone marrow transplant recipients by the adoptive transfer of CMV-specific T cell clones generated from the respective bone marrow donor.
在同种异体骨髓移植受者中，包括巨细胞病毒（CMV）感染在内的危及生命的感染的发生与移植后出现的严重且持久的免疫缺陷有关。我们实验室对骨髓移植后CMV特异性T细胞反应恢复情况进行的研究表明，CMV疾病仅发生在那些CD8 + CMV特异性T细胞反应未重建的患者中。已开发出从具有保护性免疫的健康CMV血清阳性个体中分离I类主要组织相容性复合体限制的CD8 + CMV特异性T细胞克隆的方法。从多个个体中分离出的大多数细胞毒性T细胞克隆识别被感染细胞呈递的病毒体结构蛋白，而无需病毒基因的表达。这些结果表明，这种免疫显性反应对于在健康的CMV血清阳性个体中将病毒维持在潜伏状态可能至关重要。我们机构已启动临床试验，以研究通过过继转移从相应骨髓供体产生的CMV特异性T细胞克隆来选择性重建骨髓移植受者中CMV特异性免疫的潜力。
