Hoft D F, Lynch R G, Kirchhoff L V
Department of Internal Medicine, University of Iowa, Iowa City.
J Immunol. 1993 Dec 15;151(12):7038-47.
The Tulahuén strain of Trypanosoma cruzi has been shown previously to cause higher parasitemias and greater mortality in BALB/c mice compared with C57BL6/J mice. The goal of our study was to determine whether different cytokine responses to parasite Ag during T. cruzi infection correlate with the susceptible and resistant phenotypes identified in these mice. At several time points after initial infection with insect-derived metacyclic trypomastigotes, lymph node and spleen cell suspensions were prepared from animals of each mouse strain. These lymphocyte suspensions were stimulated with Ag prepared from cultured parasites and the production of IFN-gamma, IL-4, IL-2, and IL-5 was measured. Lymphocytes from C57BL6/J mice produced 10-fold more IFN-gamma than BALB/c lymphocytes. However, this enhanced response occurred only for a limited time preceding peak parasitemias. Ag-induced secretion of IL-4 from BALB/c lymphocytes was detectable by 2 wk of infection and increased during the 2nd and 3rd mo of infection. Most C57BL6/J culture supernatants did not contain measurable levels of IL-4. Lymphocytes from both murine strains produced levels of IL-2 and IL-5 indistinguishable from uninfected controls. These results indicate that increased numbers or potency of lymphocytes that produce Ag-specific IFN-gamma responses are present in resistant mice during T. cruzi infection. This phenomenon may be responsible for the lower parasitemias seen in C57BL6/J mice. However, even these relatively resistant mice become chronically infected with T. cruzi, and spleen cells from infected mice can suppress IFN-gamma induced by heterologous Ag. Our data suggest that IL-4 production is a marker for the T. cruzi susceptible phenotype. Differential production of IL-2 or IL-5 was not found, suggesting that these cytokines are not important factors in T. cruzi resistance or susceptibility.
先前研究表明，与C57BL6/J小鼠相比，克氏锥虫的图拉韦恩株在BALB/c小鼠中可引起更高的寄生虫血症和更高的死亡率。我们研究的目的是确定在克氏锥虫感染期间，对寄生虫抗原的不同细胞因子反应是否与这些小鼠中鉴定出的易感和抗性表型相关。在用昆虫来源的循环后鞭毛体初次感染后的几个时间点，从每种小鼠品系的动物中制备淋巴结和脾细胞悬液。用培养的寄生虫制备的抗原刺激这些淋巴细胞悬液，并检测干扰素-γ、白细胞介素-4、白细胞介素-2和白细胞介素-5的产生。C57BL6/J小鼠的淋巴细胞产生的干扰素-γ比BALB/c淋巴细胞多10倍。然而，这种增强的反应仅在寄生虫血症高峰期之前的有限时间内出现。感染2周后可检测到BALB/c淋巴细胞受抗原诱导分泌白细胞介素-4，且在感染的第2和第3个月增加。大多数C57BL6/J培养上清液中白细胞介素-4的含量不可测。两种小鼠品系的淋巴细胞产生的白细胞介素-2和白细胞介素-5水平与未感染对照无差异。这些结果表明，在克氏锥虫感染期间，抗性小鼠中产生抗原特异性干扰素-γ反应的淋巴细胞数量增加或活性增强。这种现象可能是C57BL6/J小鼠中寄生虫血症较低的原因。然而，即使是这些相对抗性的小鼠也会被克氏锥虫慢性感染，且感染小鼠的脾细胞可抑制异源抗原诱导的干扰素-γ。我们的数据表明，白细胞介素-4的产生是克氏锥虫易感表型的一个标志。未发现白细胞介素-2或白细胞介素-5的差异产生，表明这些细胞因子不是克氏锥虫抗性或易感性的重要因素。
