Laboratory of Immunology, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris, University Paris VII, 48 Boulevard Sérurier, Paris, France.
Biol Blood Marrow Transplant. 2011 Apr;17(4):476-85. doi: 10.1016/j.bbmt.2010.09.010. Epub 2010 Nov 11.
The nature of adenovirus (AdV)-specific T cells that could best predict the capacity of immunocompromised host to fight AdV is unclear. To this aim, 47 pediatric patients were enrolled for at least 3 months either at allogeneic bone marrow transplantation (BMT) (23 genoidentical, 18 unrelated of which 9 were 10/10 and 9 were 9/10 HLA-matched) or at unrelated cord blood transplantation (n = 6). Enumeration of AdV-specific CD4 T cells secreting cytokines (flow cytometry) and proliferative responses to AdV ((3)HT-incorporation) were compared to AdV-DNAemia. A total of 44/47 patients did not evidence AdV-DNAemia. Thirty-two of 44 (73%) developed CD4-mediated interferon-gamma (IFN-γ) responses to AdV (median 0.36 CD4/μL of blood) since the first month post-HSCT (n = 11: 8 genoidentical and 3 unrelated) or the third month (n = 21 additional patients). At 3 months, both incidence and level intensities of AdV-specific CD4 appeared similar in genoidentical and unrelated BMT (70% and 80%; 0.36 and 0.21 CD4/μL, respectively) and not statistically different from age-matched controls (76%; 1.35 CD4/μL), whereas cord blood transplanted patients exhibited similar incidence but higher level intensities (67%; 1.49 CD4/μL). Polyfunctional (IL2 + IFN-γ) and proliferative responses appeared later, after the third month. Three of 4 9/10 HLA-matched unrelated HSCT that did not develop immunity to AdV presented chemotherapy-resistant AdV-DNAemia at 3 to 5 months post-hematopoietic stem cell transplantation (HSCT). Two were successfully treated with AdV-specific CTL infusion. Monitoring, since month 1 post-HSCT, of IFN-γ-secreting AdV-specific CD4 appears suitable for early detection of at-risk patients especially in 9/10 HLA-matched unrelated HSCT and preferable to monitoring of more delayed IL2- and proliferative responses.
腺病毒（AdV）特异性 T 细胞的性质，能够最好地预测免疫功能低下宿主抵抗 AdV 的能力，目前尚不清楚。为此，我们招募了 47 名儿科患者，他们至少在异基因骨髓移植（BMT）（23 名基因相同，18 名无关，其中 9 名 10/10，9 名 9/10 HLA 匹配）或无关脐带血移植（n=6）中接受了至少 3 个月的治疗。我们比较了 AdV 特异性 CD4 T 细胞分泌细胞因子（流式细胞术）和对 AdV 的增殖反应（（3）HT 掺入）与 AdV-DNA 血症。共有 47 名患者中的 44 名未发现 AdV-DNA 血症。在移植后第一个月（n=11：8 名基因相同，3 名无关）或第三个月（n=21 名其他患者），44 名患者中的 32 名（73%）出现 AdV 特异性 CD4 介导的干扰素-γ（IFN-γ）反应。在异基因 BMT 中，3 个月时，AdV 特异性 CD4 的发生率和水平强度均相似，在基因相同和无关 BMT 中分别为 70%和 80%（0.36 和 0.21 CD4/μL），与年龄匹配的对照组无统计学差异（76%；1.35 CD4/μL），而接受脐带血移植的患者表现出相似的发生率，但水平强度更高（67%；1.49 CD4/μL）。多能（IL2+IFN-γ）和增殖反应在第三个月后出现。3 名未对 AdV 产生免疫力的 9/10 HLA 匹配无关 BMT 在造血干细胞移植（HSCT）后 3 至 5 个月出现化疗耐药性 AdV-DNA 血症。2 例患者经 AdV 特异性 CTL 输注成功治疗。自 HSCT 后 1 个月开始，监测 IFN-γ 分泌的 AdV 特异性 CD4 似乎适合早期发现高危患者，特别是在 9/10 HLA 匹配的无关 HSCT 中，并且优于监测更延迟的 IL2 和增殖反应。
