Uzonna J E, Kaushik R S, Gordon J R, Tabel H
Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada.
Parasite Immunol. 1999 Feb;21(2):57-71. doi: 10.1046/j.1365-3024.1999.00202.x.
We studied IL-4, IL-10 and IFN-gamma secretion by splenocytes and the plasma levels of different isotypes of antibodies against various antigens of Trypanosoma congolense in highly susceptible BALB/c and relatively resistant C57BL/6 mice during the early course of infection with T. congolense. The patterns of appearance of cytokine spotforming cells in the spleens were essentially similar in the two mouse strains although higher numbers were detected in the spleens of BALB/c than C57BL/6 mice on some days post-infection. However, the amount of IL-4, IL-10 and IFN-gamma secreted into the culture fluids was dramatically different. From day 4 forward, splenocytes from BALB/c mice secreted very high levels of these cytokines. In contrast, splenocytes from infected C57BL/6 mice did not secrete detectable levels of IL-4 throughout the period tested. The secretion of IL-10 and IFN-gamma by C57BL/6 splenocytes only became appreciable on day 6 and was down-regulated by day 8, when the first wave of parasitaemia was being controlled. At days 6-8, splenocytes from infected C57BL/6 mice secreted two-fold higher amounts of IL-12 p40 than those from BALB/c mice. Infected BALB/c mice mounted an earlier IgM antibody response to variant surface glycoprotein (VSG), formalin-fixed T. congolense and whole T. congolense lysates than did infected C57BL/6 mice. However, they failed to make any detectable IgG3 and IgG2a antibody responses to these antigens whereas infected C57BL/6 mice made strong IgG3 and IgG2a responses. We speculate that enhanced resistance against T. congolense infections in mice may be mediated by IL-12 dependent synthesis of IgG2 antibodies to VSG and possibly also common trypanosomal antigens.
我们研究了在感染刚果锥虫的早期阶段，高度易感的BALB/c小鼠和相对抗性的C57BL/6小鼠脾细胞分泌白细胞介素-4（IL-4）、白细胞介素-10（IL-10）和γ干扰素（IFN-γ）的情况，以及针对刚果锥虫各种抗原的不同抗体亚型的血浆水平。尽管在感染后的某些天，BALB/c小鼠脾脏中检测到的细胞因子斑点形成细胞数量比C57BL/6小鼠脾脏中的多，但两种小鼠品系脾脏中细胞因子斑点形成细胞的出现模式基本相似。然而，分泌到培养液中的IL-4、IL-10和IFN-γ的量却有显著差异。从第4天起，BALB/c小鼠的脾细胞分泌这些细胞因子的水平非常高。相比之下，在整个测试期间，感染的C57BL/6小鼠的脾细胞未分泌可检测水平的IL-4。C57BL/6小鼠脾细胞分泌IL-10和IFN-γ的情况直到第6天才变得明显，并在第8天被下调，此时第一波虫血症正在得到控制。在第6至8天，感染的C57BL/6小鼠的脾细胞分泌的IL-12 p40量比BALB/c小鼠的脾细胞高两倍。感染的BALB/c小鼠比感染的C57BL/6小鼠对变异表面糖蛋白（VSG）、福尔马林固定的刚果锥虫和刚果锥虫全裂解物产生更早的IgM抗体反应。然而，它们未能对这些抗原产生任何可检测到的IgG3和IgG2a抗体反应，而感染的C57BL/6小鼠则产生了强烈的IgG3和IgG2a反应。我们推测，小鼠对刚果锥虫感染抵抗力的增强可能是由IL-12依赖性合成针对VSG以及可能还有常见锥虫抗原的IgG2抗体介导的。
