Rottenberg M E, Cardoni R L, Sinagra A, Riarte A, Rodriguez Nantes I, Lauricella M, Segura E L
Instituto Nacional de Diagnóstico e Investigación de la Enfermedad de Chagas Dr. M. Fatala Chabén, Buenos Aires, Argentina.
Exp Parasitol. 1991 Aug;73(2):127-36. doi: 10.1016/0014-4894(91)90016-p.
Effector mechanisms of resistance exerted by T cells from BALB/c mice chronically infected with Trypanosoma cruzi, Tulahuén strain, were studied. Spleen cells from chronically infected mice (Chro-SC) prestimulated with heat-killed trypomastigotes (HKT) and/or IL-2 destroyed PHA-labeled p-815 mastocytoma cells, HKT-pulsed macrophages, and normal peritoneal macrophages. However, HKT-stimulated Chro-SC did not affect the infectivity of free bloodstream forms of the parasite. Upon HKT stimulation, Chro-SC or their culture supernatant activated peritoneal macrophages for the destruction of intracellular amastigotes. The effect was abolished after Thy 1.2+ cell depletion. The addition of Cyclosporin A (CyA), which blocks T-cell activation, during HKT-stimulation of Chro-SC, diminished their ability to activate the trypanocidal activity of macrophages. CyA also inhibited the production of both macrophage-activating factors and interferon-gamma by HKT-stimulated Chro-SC. CyA administration to recipients of nylon-wool nonadherent spleen cells from chronically infected mice inhibited their adoptively acquired resistance against T. cruzi, suggesting that the conferred resistance depended on the effect of specifically activated cells. When administered during the chronic stage of the infection, CyA abrogated the antigen-specific delayed type hypersensitivity response but increased the levels of anti-T. cruzi IgG antibodies. Neither parasitemia, tissular parasitism in myocardium or skeletal muscle, nor mortality were detected after CyA treatment, suggesting the presence of a CyA nonsensitive mechanism(s) in the control of T. cruzi during the chronic phase of the infection.
研究了感染克氏锥虫图拉韦恩株的BALB/c小鼠的T细胞所产生的抗性效应机制。用热灭活的锥鞭毛体（HKT）和/或白细胞介素-2预刺激的慢性感染小鼠的脾细胞（Chro-SC）可破坏PHA标记的p-815肥大细胞瘤细胞、HKT脉冲巨噬细胞和正常腹膜巨噬细胞。然而，HKT刺激的Chro-SC并不影响寄生虫游离血流形式的感染性。经HKT刺激后，Chro-SC或其培养上清液可激活腹膜巨噬细胞以破坏细胞内无鞭毛体。Thy 1.2+细胞耗竭后，该效应消失。在Chro-SC的HKT刺激过程中添加阻断T细胞活化的环孢素A（CyA），会降低其激活巨噬细胞杀锥虫活性的能力。CyA还抑制了HKT刺激的Chro-SC产生巨噬细胞活化因子和干扰素-γ。对接受慢性感染小鼠尼龙毛非黏附脾细胞的受体给予CyA，可抑制其对克氏锥虫的过继性获得抗性，这表明所赋予的抗性取决于特异性活化细胞的作用。在感染的慢性阶段给予CyA时，可消除抗原特异性迟发型超敏反应，但会增加抗克氏锥虫IgG抗体的水平。CyA治疗后未检测到寄生虫血症、心肌或骨骼肌中的组织寄生虫感染以及死亡率，这表明在感染的慢性期，存在一种对CyA不敏感的机制来控制克氏锥虫。
