Gabanti Elisa, Bruno Francesca, Lilleri Daniele, Fornara Chiara, Zelini Paola, Cane Ilaria, Migotto Clara, Sarchi Eleonora, Furione Milena, Gerna Giuseppe
Laboratori Sperimentali di Ricerca, Area Trapiantologica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Divisione di Nefrologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
PLoS One. 2014 Aug 28;9(8):e106044. doi: 10.1371/journal.pone.0106044. eCollection 2014.
In solid-organ transplant recipients (SOTR) the protective role of human cytomegalovirus (HCMV)-specific CD4+, CD8+ and γδ T-cells vs. HCMV reactivation requires better definition. The aim of this study was to investigate the relevant role of HCMV-specific CD4+, CD8+ and γδ T-cells in different clinical presentations during the post-transplant period. Thirty-nine SOTR underwent virologic and immunologic follow-up for about 1 year after transplantation. Viral load was determined by real-time PCR, while immunologic monitoring was performed by measuring HCMV-specific CD4+ and CD8+ T cells (following stimulation with autologous HCMV-infected dendritic cells) and γδ T-cells by flow cytometry. Seven patients had no infection and 14 had a controlled infection, while both groups maintained CD4+ T-cell numbers above the established cut-off (0.4 cell/µL blood). Of the remaining patients, 9 controlled the infection temporarily in the presence of HCMV-specific CD8+ only, until CD4+ T-cell appearance; while 9 had to be treated preemptively due to a viral load greater than the established cut-off (3×10(5) DNA copies/mL blood) in the absence of specific CD4+ T-cells. Polyfunctional CD8+ T-cells as well as Vδ2- γδ T-cells were not associated with control of infection. In conclusion, in the absence of HCMV-specific CD4+ T-cells, no long-term protection is conferred to SOTR by either HCMV-specific CD8+ T-cells alone or Vδ2- γδ T-cell expansion.
在实体器官移植受者(SOTR)中,人巨细胞病毒(HCMV)特异性CD4⁺、CD8⁺和γδ T细胞对HCMV再激活的保护作用尚需更明确的定义。本研究旨在探讨HCMV特异性CD4⁺、CD8⁺和γδ T细胞在移植后不同临床表现中的相关作用。39例SOTR在移植后接受了约1年的病毒学和免疫学随访。通过实时PCR测定病毒载量,通过流式细胞术测量HCMV特异性CD4⁺和CD8⁺ T细胞(用自体HCMV感染的树突状细胞刺激后)以及γδ T细胞进行免疫学监测。7例患者未发生感染,14例患者感染得到控制,两组的CD4⁺ T细胞数量均维持在既定临界值(0.4个细胞/μL血液)以上。其余患者中,9例仅在存在HCMV特异性CD8⁺ T细胞的情况下暂时控制了感染,直至CD4⁺ T细胞出现;而9例患者由于在缺乏特异性CD4⁺ T细胞的情况下病毒载量大于既定临界值(3×10⁵ DNA拷贝/mL血液)而不得不接受抢先治疗。多功能CD8⁺ T细胞以及Vδ2⁻γδ T细胞与感染控制无关。总之,在缺乏HCMV特异性CD4⁺ T细胞的情况下,单独的HCMV特异性CD8⁺ T细胞或Vδ2⁻γδ T细胞扩增均不能为SOTR提供长期保护。