Ungeheuer M, Elissa N, Morelli A, Georges A J, Deloron P, Debre P, Bain O, Millet P
Centre International de Recherches Médicales de Franceville, Franceville, Gabon.
Parasite Immunol. 2000 Apr;22(4):173-83. doi: 10.1046/j.1365-3024.2000.00291.x.
In order to shed light on the mechanisms of antifilarial protective immunity, we investigated the course of experimental loaiosis after vaccination in a nonhuman primate host, Mandrillus sphinx. Six vaccinated (V) mandrills received 50 irradiated L3 while six nonvaccinated (NV) received saline solution on days -60, -30 and -15. All animals were challenged with 100 intact L3 (day 0). Parasitological and immunological status were followed for 9 months. Vaccination delayed the appearance and mean peak of microfilaraemia. Five mandrills (Mf-) were never microfilaraemic (one V mandrill) or microfilaraemic on only one occasion (2 V and 2 NV), the other seven having stable microfilaraemia (Mf+). The cytokine response of peripheral blood mononuclear cells to L3 (L3 Ag) was Th2 dominated, while microfilariae (Mf Ag) elicited a Th0-like response. During vaccination, Th2 cytokine production significantly increased in V mandrills against L3 Ag, as well as Mf Ag, whereas Th1 cytokines decreased. On day 60 postinoculation, cellular proliferation was higher in V mandrills in response to L3 and Mf Ags and PHA-L mitogen. At the end of prepatency (on day 130), mandrills with delayed appearance of microfilaraemia exhibited a high, transient IL-2 and IL-4 secretion in response to L3 Ag. Finally, high anti-Mf Th2 cytokine levels characterized Mf-mandrills not only during prepatency, but also (for IL-5) before immunization. However, the presence of a balanced Th1 anti-L3 response during prepatency in the amicrofilaraemic mandrill suggests its importance in protective immunity. Taken together, our data suggest that Th2 cells and also Th1 components of the antifilarial response, especially to larval antigen, may contribute to parasite elimination.
为了阐明抗丝虫保护性免疫的机制，我们在一种非人类灵长类宿主——狮尾狒（Mandrillus sphinx）中研究了疫苗接种后实验性罗阿丝虫病的病程。6只接种疫苗（V）的狮尾狒在第-60、-30和-15天接受了50条辐照的L3幼虫，而6只未接种疫苗（NV）的狮尾狒接受了生理盐水。所有动物在第0天接受100条完整的L3幼虫攻击。对寄生虫学和免疫学状况进行了9个月的跟踪观察。疫苗接种延迟了微丝蚴血症的出现和平均峰值。5只狮尾狒（Mf-）从未出现微丝蚴血症（1只接种疫苗的狮尾狒）或仅在一次出现微丝蚴血症（2只接种疫苗的和2只未接种疫苗的），另外7只具有稳定的微丝蚴血症（Mf+）。外周血单核细胞对L3（L3抗原）的细胞因子反应以Th2为主，而对微丝蚴（Mf抗原）的反应则引发类似Th0的反应。在疫苗接种期间，接种疫苗的狮尾狒针对L3抗原以及Mf抗原的Th2细胞因子产生显著增加，而Th1细胞因子减少。接种后第60天，接种疫苗的狮尾狒对L3和Mf抗原以及PHA-L丝裂原的细胞增殖更高。在潜伏期结束时（第130天），微丝蚴血症出现延迟的狮尾狒对L3抗原表现出高且短暂的IL-2和IL-4分泌。最后，高抗Mf Th2细胞因子水平不仅在潜伏期，而且（对于IL-5）在免疫前就表征了Mf-狮尾狒。然而，在无微丝蚴血症的狮尾狒潜伏期存在平衡的Th1抗L3反应表明其在保护性免疫中的重要性。综上所述，我们的数据表明Th2细胞以及抗丝虫反应的Th1成分，尤其是对幼虫抗原的反应，可能有助于消除寄生虫。
