Reis E A G, Azevedo T M, McBride A J A, Harn D A, Reis M G
Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Bahia, Brazil.
Scand J Immunol. 2007 Dec;66(6):662-70. doi: 10.1111/j.1365-3083.2007.02024.x.
Schistosome infection induces profound Th-biasing and immune suppression. Although much has been examined in mice, few studies have examined responses of naïve humans to schistosome antigens. In this study, we examined the response of naïve human peripheral blood mononuclear cells (nPBMC) to stimulation with Schistosoma mansoni soluble egg antigen (SEA) using a priming in vitro (PIV) assay. We found that SEA induced a pronounced CD4+ T-helper cell response based on cytokine secretion and phenotyping markers. SEA-stimulated nPBMC (SEA cells) at day 7 post-priming and after the first recall consisted predominantly of Th0-like CD4+ T cells. Following the second recall, the majority of donor (10/12) responses were Th2-like. The cell population consisted of approximately 64% CD4+, 17% CD8(+high), 12% CD19+, and 7% CD23+ cells. The CD4+ population also expressed HLA-DR+, CD54+, CD45RO+ and CD25+ whereas the CD19+ cells expressed CD80 and CD86. Following priming, we detected high levels of IL-6, IFN-gamma, IL-12p40, IL-10 and IL-5. Upon restimulation, SEA cells secreted IL-5 and high levels of IL-10, typical of a Th2-like response. The data presented herein shows that the majority of naïve donor dendritic cells, following stimulation with SEA, prime and clonally expand SEA-specific T cells towards a Th2-type response. However, two donors responded with an atypical response, producing IFN-gamma coincident with low levels of IL-10. Whether this differential response was due to HLA or other genes was not determined but is currently under investigation.
血吸虫感染会引发显著的Th偏向和免疫抑制。尽管在小鼠身上已进行了大量研究，但很少有研究检测过未接触过血吸虫的人类对血吸虫抗原的反应。在本研究中，我们使用体外致敏（PIV）试验检测了未接触过血吸虫的人外周血单个核细胞（nPBMC）对曼氏血吸虫可溶性虫卵抗原（SEA）刺激的反应。我们发现，基于细胞因子分泌和表型标记，SEA可诱导明显的CD4+辅助性T细胞反应。致敏后第7天以及首次再次刺激后，SEA刺激的nPBMC（SEA细胞）主要由Th0样CD4+ T细胞组成。第二次再次刺激后，大多数供体（10/12）的反应为Th2样。细胞群体由约64%的CD4+、17%的CD8(+高)、12%的CD19+和7%的CD23+细胞组成。CD4+群体还表达HLA-DR+、CD54+、CD45RO+和CD25+，而CD19+细胞表达CD80和CD86。致敏后，我们检测到高水平的IL-6、IFN-γ、IL-12p40、IL-10和IL-5。再次刺激后，SEA细胞分泌IL-5和高水平的IL-10，这是Th2样反应的典型特征。本文提供的数据表明，大多数未接触过血吸虫的供体树突状细胞在受到SEA刺激后，会使SEA特异性T细胞致敏并克隆扩增，使其向Th2型反应发展。然而，有两名供体出现了非典型反应，产生IFN-γ的同时IL-10水平较低。这种差异反应是由于HLA还是其他基因尚未确定，但目前正在研究中。
