Lalonde R G, Ali-Khan Z, Tanowitz H B
Exp Parasitol. 1985 Feb;59(1):33-43. doi: 10.1016/0014-4894(85)90054-2.
The outcome of Trypanosoma cruzi infection in inbred strains of mice is under genetic control. The lymphocyte responses to T-cell mitogens and their regulation were investigated in strains of mice resistant or susceptible to T. cruzi. Six to eight days after the inoculation of T. cruzi, resistant and susceptible mice had depressed responses to T-cell mitogens. In resistant B6 mice, suppression was maximal 18 days after infection and it persisted for at least 320 days. The duration of immunosuppression correlated with the persistence of a subpatent parasitemia. In cell mixing experiments, it was determined that the concanavalin A (Con A) responses in the resistant B6 and B6C3F1 mouse strains were suppressed by highly active T-suppressor cells. In the susceptible C3H mice, intense suppression of the Con A responses was detected 14 days after inoculation of T. cruzi. Nevertheless, only weak suppressor cell activity was detected in the infected C3H mice, and suppression was not abrogated by passage through a nylon wool column nor by treatment with antitheta antibodies and complement. Thus, it was suggested that, during the course of infection with T. cruzi, splenic T cells from C3H mice acquired a block in the metabolic pathway for cellular activation by Con A. The influences of T. cruzi epimastigotes on the Con A responses of spleen cells from uninfected mice were then studied. The Con A responses of spleen cells from C3H mice were depressed in the presence of epimastigotes, whereas they were either unaffected or enhanced in spleen cells from B6 mice. Hence, the immunoregulatory events provoked by T. cruzi infection differed in genetically resistant and susceptible mice, and lymphocytes from C3H mice were predisposed to a parasite-induced block in the responses to Con A. Thus, the gene(s) determining the outcome of infection with T. cruzi may be phenotypically expressed through an influence on immunoregulatory events.
克氏锥虫感染近交系小鼠的结果受遗传控制。对克氏锥虫具有抗性或易感性的小鼠品系中淋巴细胞对T细胞有丝分裂原的反应及其调节进行了研究。接种克氏锥虫6至8天后，抗性和易感小鼠对T细胞有丝分裂原的反应均降低。在抗性B6小鼠中，感染后18天抑制作用最大，并持续至少320天。免疫抑制的持续时间与亚临床期寄生虫血症的持续时间相关。在细胞混合实验中，确定抗性B6和B6C3F1小鼠品系中刀豆球蛋白A（Con A）反应受到高活性T抑制细胞的抑制。在易感的C3H小鼠中，接种克氏锥虫14天后检测到Con A反应受到强烈抑制。然而，在感染的C3H小鼠中仅检测到微弱的抑制细胞活性，并且通过尼龙毛柱传代或用抗θ抗体和补体处理均不能消除抑制作用。因此，有人提出，在克氏锥虫感染过程中，C3H小鼠的脾T细胞在Con A介导的细胞活化代谢途径中出现了阻断。随后研究了克氏锥虫前鞭毛体对未感染小鼠脾细胞Con A反应的影响。在存在前鞭毛体的情况下，C3H小鼠脾细胞的Con A反应受到抑制，而B6小鼠脾细胞的Con A反应要么未受影响要么增强。因此，克氏锥虫感染引发的免疫调节事件在遗传抗性和易感小鼠中有所不同，并且C3H小鼠的淋巴细胞在对Con A的反应中易受寄生虫诱导的阻断。因此，决定克氏锥虫感染结果的基因可能通过对免疫调节事件的影响在表型上得以表达。
