Department of Paediatric Immunology and Haematology, University Medical Centre Utrecht, Wilhelmina Children's Hospital Utrecht, The Netherlands.
Clin Immunol. 2013 Mar;146(3):228-39. doi: 10.1016/j.clim.2013.01.002. Epub 2013 Jan 16.
Adenoviruses (HAdV) can cause life threatening infections, especially in paediatric patients after allogeneic stem cell transplantation (SCT). Yet, no effective antiviral medication is available. One treatment option is adoptive transfer of HAdV-specific T-cells from the graft donor into the patient. Especially CD4+ T-cells are critical to control HAdV infection. To allow for applicability of CD4+ T-cells in adoptive therapy, sufficient numbers of HAdV-specific T-cells with low levels of residual alloreactive T-cells are required. In this study, we explored the possibility to selectively expand and isolate functional HAdV-specific T-cells from PBMCs in response to 15-mer peptides using artificial antigen-presenting cells (aAPCs), composed of liposomes harbouring HAdV-peptide/HLA-Class-II complexes. HAdV-specific T-cells generated using this method produce mainly pro-inflammatory cytokines, express perforin and granzyme B, kill HAdV-infected cells effectively and are not alloreactive. Thus, the generation and isolation of HAdV-specific CD4+ T-cells seem a critical step towards specific adoptive therapy for HAdV infections after allogeneic SCT.
腺病毒（HAdV）可导致危及生命的感染，尤其是在异基因干细胞移植（SCT）后的儿科患者中。然而，目前尚无有效的抗病毒药物。一种治疗选择是从供体移植物向患者中输注 HAdV 特异性 T 细胞。特别是 CD4+ T 细胞对于控制 HAdV 感染至关重要。为了使 CD4+ T 细胞在过继性治疗中具有适用性，需要有足够数量的低残留同种反应性 T 细胞的 HAdV 特异性 T 细胞。在这项研究中，我们探索了使用人工抗原呈递细胞（aAPC），由携带 HAdV-肽/HLA 类 II 复合物的脂质体组成，从 PBMC 中选择性扩增和分离针对 15 肽的功能性 HAdV 特异性 T 细胞的可能性。使用这种方法产生的 HAdV 特异性 T 细胞主要产生促炎细胞因子，表达穿孔素和颗粒酶 B，有效杀伤 HAdV 感染的细胞，并且无同种反应性。因此，HAdV 特异性 CD4+ T 细胞的产生和分离似乎是异基因 SCT 后针对 HAdV 感染的特异性过继性治疗的关键步骤。
