Tzannou Ifigeneia, Nicholas Sarah K, Lulla Premal, Aguayo-Hiraldo Paibel I, Misra Anisha, Martinez Caridad A, Machado Annette A, Orange Jordan S, Piedra Pedro A, Vera Juan F, Leen Ann M
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, and Houston Methodist Hospital.
Solid Organ Transplant Immunology, Section of Immunology, Allergy and Rheumatology.
J Infect Dis. 2017 Sep 15;216(6):678-687. doi: 10.1093/infdis/jix358.
Human metapneumovirus (hMPV) is a respiratory virus detected in ≥9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients, in whom it can cause significant morbidity and mortality. Given the lack of effective antivirals, we investigated the potential for immunotherapeutic intervention, using adoptively transferred T cells. Thus, we characterized the cellular immune response to the virus and identified F, N, M2-1, M, and P as immunodominant target antigens. Reactive T cells were polyclonal (ie, they expressed CD4 and CD8), T-helper type 1 polarized, and polyfunctional (ie, they produced interferon γ, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, and granzyme B), and they were able to kill autologous antigen-loaded targets. The detection of hMPV-specific T cells in HSCT recipients who endogenously controlled active infections support the clinical importance of T-cell immunity in mediating protective antiviral effects. Our results demonstrate the feasibility of developing an immunotherapy for immunocompromised patients with uncontrolled infections.
人偏肺病毒（hMPV）是一种在≥9%的异基因造血干细胞移植（HSCT）受者中检测到的呼吸道病毒，在这些受者中它可导致显著的发病率和死亡率。鉴于缺乏有效的抗病毒药物，我们研究了采用过继转移T细胞进行免疫治疗干预的可能性。因此，我们对针对该病毒的细胞免疫反应进行了表征，并确定F、N、M2-1、M和P为免疫显性靶抗原。反应性T细胞是多克隆的（即它们表达CD4和CD8），呈1型辅助性T细胞极化，且具有多功能（即它们产生干扰素γ、肿瘤坏死因子α、粒细胞-巨噬细胞集落刺激因子和颗粒酶B），并且它们能够杀伤负载自体抗原的靶细胞。在对内源性控制活动性感染的HSCT受者中检测到hMPV特异性T细胞，支持了T细胞免疫在介导保护性抗病毒作用中的临床重要性。我们的结果证明了为感染未得到控制的免疫受损患者开发免疫疗法的可行性。
