Bourguin I, Moser M, Buzoni-Gatel D, Tielemans F, Bout D, Urbain J, Leo O
CJF INSERM 93-09 d'Immunologie des Maladies Infectieuses, Equipe Associée INRA d'Immunologie Parasitaire, U.F.R. des Sciences Pharmaceutiques, 37200 Tours, France.
Infect Immun. 1998 Oct;66(10):4867-74. doi: 10.1128/IAI.66.10.4867-4874.1998.
The activation of a predominant T-helper-cell subset plays a critical role in disease resolution. In the case of Toxoplasma gondii, the available evidence indicates that CD4(+) protective cells belong to the Th1 subset. The aim of this study was to determine whether T. gondii antigens (in T. gondii sonicate [TSo]) presented by splenic dendritic cells (DC) were able to induce a specific immune response in vivo and to protect CBA/J mice orally challenged with T. gondii cysts. CBA/J mice immunized with TSo-pulsed DC exhibited significantly fewer cysts in their brains after oral infection with T. gondii 76K than control mice did. Protected mice developed a strong humoral response in vivo, with especially high levels of anti-TSo immunoglobulin G2a antibodies in serum. T. gondii antigens such as SAG1 (surface protein), SAG2 (surface protein), MIC1 (microneme protein), ROP2 through ROP4 (rhoptry proteins), and MIC2 (microneme protein) were recognized predominantly. Furthermore, DC loaded with TSo, which synthesized high levels of interleukin-12 (IL-12), triggered a strong cellular response in vivo, as assessed by the proliferation of lymph node cells in response to TSo restimulation in vitro. Cellular proliferation was associated with gamma interferon and IL-2 production. Taken together, these results indicate that immunization of CBA/J mice with TSo-pulsed DC can induce both humoral and Th1-like cellular immune responses and affords partial resistance against the establishment of chronic toxoplasmosis.
优势性辅助性T细胞亚群的激活在疾病的消退中起着关键作用。就刚地弓形虫而言，现有证据表明CD4(+)保护性细胞属于Th1亚群。本研究的目的是确定脾脏树突状细胞（DC）呈递的刚地弓形虫抗原（在刚地弓形虫超声裂解物 [TSo] 中）是否能够在体内诱导特异性免疫反应，并保护经刚地弓形虫包囊口服攻击的CBA/J小鼠。用TSo脉冲DC免疫的CBA/J小鼠在经刚地弓形虫76K口服感染后，其脑中的包囊明显少于对照小鼠。受保护的小鼠在体内产生了强烈的体液反应，血清中抗TSo免疫球蛋白G2a抗体水平尤其高。主要识别出刚地弓形虫抗原，如SAG1（表面蛋白）、SAG2（表面蛋白）、MIC1（微线体蛋白）、ROP2至ROP4（棒状体蛋白）和MIC2（微线体蛋白）。此外，负载TSo且合成高水平白细胞介素-12（IL-12）的DC在体内引发了强烈的细胞反应，这通过体外经TSo再刺激后淋巴结细胞的增殖来评估。细胞增殖与γ干扰素和IL-2的产生相关。综上所述，这些结果表明用TSo脉冲DC免疫CBA/J小鼠可诱导体液和Th1样细胞免疫反应，并对慢性弓形虫病的发生提供部分抗性。
