Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110 029, India.
Vaccine. 2013 Mar 25;31(13):1707-16. doi: 10.1016/j.vaccine.2013.01.041. Epub 2013 Feb 4.
Defensin peptides have their direct role in host defense against microbial infection as innate molecules and also thought to contribute to adaptive immunity by recruiting naïve T-cells and immature dendritic cells at the site of infection through CCR6 receptor. The main aim of the present study is to investigate the efficacy of defensins for the induction of cell mediated immune response against the peptide antigen of HIV-1 encapsulated in PLG microparticles through intranasal (IN) route in mice model. To characterized, we have analyzed T-cell proliferation, Th1/Th2 cytokines, β-chemokines production and IFN-γ/perforin secretion from CD4(+)/CD8(+) T-cells in response to HIV immunogen alone and with defensins at different mucosal site i.e. lamina propria (LP), spleen (SP) and peyer's patches (PP). The cellular immunogenicity of HIV peptide with defensin formulations showed a significantly higher (p<0.001) proliferation response as compared to individual HIV peptide. The enhanced cytokines measurement profile showed mixed Th1 and Th2 type of peptide specific immune response by the incorporation of defensins. In the continuation, enhancement in MIP-1α and RANTES level was also observed in HIV peptide-defensin formulations. The FACS data had revealed that CD4(+)/CD8(+) T-cells showed significantly (p<0.001) higher IFN-γ and perforin secretion in HIV with defensin peptide formulations than HIV antigen alone group. Thus, the study emphasized here that defensin peptides have a potential role as mucosal adjuvant, might be responsible for the induction of cell mediated immunity when administered in mice through IN route with HIV peptide antigen.
防御素肽作为先天分子,在宿主抵御微生物感染中发挥直接作用,并且通过 CCR6 受体在感染部位募集幼稚 T 细胞和未成熟树突状细胞,被认为有助于适应性免疫。本研究的主要目的是研究防御素在通过鼻腔(IN)途径在小鼠模型中诱导针对 HIV-1 肽抗原的细胞介导免疫反应的功效,该肽抗原被包裹在 PLG 微颗粒中。为了进行分析,我们已经分析了 T 细胞增殖、Th1/Th2 细胞因子、β-趋化因子产生以及 CD4(+)/CD8(+)T 细胞对 HIV 免疫原的 IFN-γ/穿孔素分泌,单独使用和与防御素一起使用时在不同的粘膜部位,即固有层 (LP)、脾脏 (SP) 和派尔氏斑 (PP)。与单独的 HIV 肽相比,防御素配方中的 HIV 肽的细胞免疫原性显示出显著更高的 (p<0.001) 增殖反应。增强的细胞因子测量谱显示,通过防御素的掺入,产生了混合的 Th1 和 Th2 型肽特异性免疫反应。此外,在 HIV 肽-防御素配方中也观察到 MIP-1α 和 RANTES 水平的增强。FACS 数据显示,与单独的 HIV 抗原组相比,CD4(+)/CD8(+)T 细胞在 HIV 与防御素肽配方中显示出显著更高的 IFN-γ 和穿孔素分泌 (p<0.001)。因此,本研究强调了防御素肽作为粘膜佐剂的潜力,当通过 IN 途径与 HIV 肽抗原一起在小鼠中给药时,可能会负责诱导细胞介导的免疫。