Lee Byeong Cheol, O'Sullivan Insug, Kim Eugene, Park Sang Gyu, Hwang Seung Yong, Cho Daeho, Kim Tae Sung
School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
Immunology. 2009 Jan;126(1):84-91. doi: 10.1111/j.1365-2567.2008.02880.x. Epub 2008 Jun 10.
T helper type 1 (Th1) cell-mediated immune responses contribute to host defences against intracellular pathogen infections and cancer. Previously, we found that aminoacyl tRNA synthetase-interacting multifunctional protein 1 (AIMP1) activated macrophages and dendritic cells to enhance Th1 responses. Herein, we manipulated this property to improve Th1 immune responses in vivo by constructing a mammalian expression plasmid (pAnti-CD3sFv/AIMP1) encoding AIMP1 fused to the anti-CD3 single-chain Fv (sFv), the smallest unit of the antibody that interacts with the CD3epsilon region of the T-cell receptor. Intramuscular injection of ovalbumin (OVA)-sensitized BALB/c mice with pAnti-CD3sFv/AIMP1 DNA adjuvant increased the OVA-specific, interferon-gamma production by their CD4(+) T cells and the levels of anti-OVA immunoglobulin G2a (IgG2a) isotype in their sera. Furthermore, the pAnti-CD3sFv/AIMP1 DNA adjuvant decreased interleukin-4 production and anti-OVA IgE levels in the OVA-injected mice. Importantly, the pAnti-CD3sFv/AIMP1 was more efficient than a mixture of pAnti-CD3sFv and pAIMP1 in inducing OVA-specific Th1 immune responses and also in inhibiting OVA-specific Th2 responses during antigen priming. These studies indicated that the pAnti-CD3sFv/AIMP1 fusion DNA adjuvant enhanced Th1 immune responses in antigen-sensitized mice.
1型辅助性T细胞(Th1)介导的免疫反应有助于宿主抵御细胞内病原体感染和癌症。此前,我们发现氨酰基tRNA合成酶相互作用多功能蛋白1(AIMP1)可激活巨噬细胞和树突状细胞,增强Th1反应。在此,我们通过构建一种哺乳动物表达质粒(pAnti-CD3sFv/AIMP1)来利用这一特性,该质粒编码与抗CD3单链Fv(sFv)融合的AIMP1,抗CD3单链Fv是与T细胞受体的CD3ε区域相互作用的抗体最小单位。用pAnti-CD3sFv/AIMP1 DNA佐剂对卵清蛋白(OVA)致敏的BALB/c小鼠进行肌肉注射,可增加其CD4(+) T细胞产生的OVA特异性干扰素-γ以及血清中抗OVA免疫球蛋白G2a(IgG2a)同种型的水平。此外,pAnti-CD3sFv/AIMP1 DNA佐剂可降低OVA注射小鼠中白细胞介素-4的产生和抗OVA IgE水平。重要的是,在抗原启动过程中,pAnti-CD3sFv/AIMP1在诱导OVA特异性Th1免疫反应以及抑制OVA特异性Th2反应方面比pAnti-CD3sFv和pAIMP1的混合物更有效。这些研究表明,pAnti-CD3sFv/AIMP1融合DNA佐剂可增强抗原致敏小鼠的Th1免疫反应。