Taylor-Robinson A W, Phillips R S
Wellcome Laboratories for Experimental Parasitology, University of Glasgow, United Kingdom.
Infect Immun. 1994 Jun;62(6):2490-8. doi: 10.1128/iai.62.6.2490-2498.1994.
The induction of T-helper cell subsets during the course of blood stage Plasmodium chabaudi chabaudi infection was compared in immunologically intact NIH mice and mice that were depleted of B cells from birth by treatment with anti-mu antibodies. For intact mice, in which the acute primary parasitemia peaked 10 days following infection, purified splenic CD4+ T cells recovered during the ascending parasitemia produced high levels in vitro of interleukin 2 (IL-2) (peak levels on day 10) and gamma interferon (IFN-gamma) (peak levels on day 7). Sera collected from these mice at around this time contained relatively high levels of P. c. chabaudi-specific immunoglobulin 2a (peak levels on day 12), and serum nitric oxide activity was significantly elevated at peak parasitemia. During the descending primary parasitemia, production of IFN-gamma and IL-2 decreased, while levels of IL-4 and IL-10 produced by splenic CD4+ T cells were significantly raised from the time at which subpatency was recorded (day 17) and persisted for at least 50 days. This was concomitant with a significant increase in levels of parasite-specific immunoglobulin G1, which peaked at around the time of recrudescence. Thus, in normal mice, sequential appearance of Th1 and Th2 responses was observed. In contrast, in B-cell-depleted mice, recovery from acute primary parasitemia was followed by a persistent patent infection which did not drop below 0.1% for at least 75 days after initiation of infection. These mice were unable to mount a significant Th2 response, manifest as an enduring inability of splenic CD4+ T cells to produce significant levels of IL-4 and IL-10. IL-2 and IFN-gamma levels remained significantly elevated throughout the 50-day observation period, and there was sustained production of nitric oxide. These data show that immune responses mediated by CD4+ T cells of the Th1 subset are capable of limiting infection beyond the initial acute phase, but that they do not eliminate parasitemia. Furthermore, as the progression from a Th1-regulated to a Th2-regulated immune response fails to occur in B-cell-depleted mice, the data suggest that B cells are required for the downregulation of Th1-mediated and/or the generation of Th2-mediated protective immunity to P. c. chabaudi.
在血液期沙氏疟原虫感染过程中，对免疫健全的NIH小鼠以及通过抗μ抗体处理从出生起就缺乏B细胞的小鼠体内辅助性T细胞亚群的诱导情况进行了比较。对于免疫健全的小鼠，急性原发性寄生虫血症在感染后10天达到峰值，在寄生虫血症上升期间回收的纯化脾CD4⁺ T细胞在体外产生高水平的白细胞介素2（IL - 2）（第10天达到峰值）和γ干扰素（IFN - γ）（第7天达到峰值）。大约在这个时候从这些小鼠收集的血清中含有相对高水平的沙氏疟原虫特异性免疫球蛋白2a（第12天达到峰值），并且在寄生虫血症峰值时血清一氧化氮活性显著升高。在原发性寄生虫血症下降期间，IFN - γ和IL - 2的产生减少，而脾CD4⁺ T细胞产生的IL - 4和IL - 10水平从记录到亚临床期（第17天）时开始显著升高，并持续至少50天。这与寄生虫特异性免疫球蛋白G1水平的显著增加同时发生，其在复发时达到峰值。因此，在正常小鼠中，观察到了Th1和Th2反应的相继出现。相比之下，在缺乏B细胞的小鼠中，从急性原发性寄生虫血症中恢复后接着是持续的显性感染，在感染开始后至少75天内寄生虫血症不低于0.１％。这些小鼠无法产生显著的Th2反应，表现为脾CD4⁺ T细胞持续无法产生显著水平的IL - 4和IL - 10。在整个50天的观察期内，IL - 2和IFN - γ水平仍显著升高，并且一氧化氮持续产生。这些数据表明，由Th1亚群的CD4⁺ T细胞介导的免疫反应能够在初始急性期之后限制感染，但它们并不能消除寄生虫血症。此外，由于在缺乏B细胞的小鼠中未能发生从Th1调节的免疫反应向Th2调节的免疫反应的转变，数据表明B细胞对于下调Th1介导的免疫反应和/或产生针对沙氏疟原虫的Th2介导的保护性免疫是必需的。
