Department of Paediatrics & Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Room L7-58, 7/F Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong, China.
J Clin Immunol. 2012 Jun;32(3):421-9. doi: 10.1007/s10875-011-9639-y.
Influenza virus is a potential cause of severe disease in the immunocompromised. X-linked agammaglobulinemia(XLA) is a primary immunodeficiency characterized by the lack of immunoglobulin, B cells, and plasma cells,secondary to mutation in Bruton’s tyrosine kinase (Btk) gene. Btk is expressed in both B and dendritic cells (DC). However, little is known about the immune response of DC and T cells to influenza virus in XLA patients.
The in vitro maturation and antigen presenting function of monocyte-derived immature DC (im DC) from 12 XLA patients and 23 age-matched normal controls in response to influenza virus were examined. Influenza virus specific CD4 and CD8 T cell responses in the patients and controls were further determined after administration of inactivated trivalent influenza vaccine.
im DC from XLA patients had normal maturation based on major histocompatibility complex (MHC)-I, MHCII, CD83 and CD86 expression, and interferon (IFN)-α and interleukin-12 production upon influenza virus stimulation.They also had a normal capacity to induce allogeneic T cell proliferation in response to influenza virus. TIV was well tolerated in XLA patients. Influenza virus-specific CD4+IFN-γ+ and CD8+ IFN-γ+ T cells and HLA-A2/M158–66-tetramer+ CTLs could be induced by TIV in XLA patients, and the levels and duration of maintaining these virus-specific cells in XLA patients are comparable to that in normal controls.
We demonstrated for the first time that XLA patients have fully competent DC and T cell immune responses to influenza virus. TIV is safe and could be an option for providing T cell-mediated protection against influenza virus infection in XLA patients.
流感病毒是免疫功能低下人群发生严重疾病的潜在原因。X 连锁无丙种球蛋白血症(XLA)是一种原发性免疫缺陷病,其特征是由于 Bruton 酪氨酸激酶(Btk)基因突变,导致免疫球蛋白、B 细胞和浆细胞缺失。Btk 在 B 细胞和树突状细胞(DC)中均有表达。然而,对于 XLA 患者中 DC 和 T 细胞对流感病毒的免疫反应知之甚少。
检测了 12 例 XLA 患者和 23 例年龄匹配的正常对照者的单核细胞来源的未成熟 DC(imDC)对流感病毒的体外成熟和抗原呈递功能。在给予灭活三价流感疫苗后,进一步确定了患者和对照组中流感病毒特异性 CD4 和 CD8 T 细胞反应。
XLA 患者的 imDC 在流感病毒刺激后,主要组织相容性复合体(MHC)-I、MHCII、CD83 和 CD86 表达以及干扰素(IFN)-α和白细胞介素-12 的产生正常。它们也具有正常的诱导针对流感病毒的同种异体 T 细胞增殖的能力。TIV 在 XLA 患者中耐受性良好。XLA 患者可通过 TIV 诱导产生流感病毒特异性 CD4+IFN-γ+和 CD8+IFN-γ+T 细胞和 HLA-A2/M158–66-四聚体+CTL,且这些病毒特异性细胞在 XLA 患者中的水平和维持时间与正常对照组相当。
我们首次证明 XLA 患者对流感病毒具有完全有效的 DC 和 T 细胞免疫反应。TIV 是安全的,可为 XLA 患者提供针对流感病毒感染的 T 细胞介导的保护。