ROLE OF ENDOGENOUS GAMMA-INTERFERON IN HOST RESPONSE TO INFECTION WITH BLOOD-STAGE PLASMODIUM-CHABAUDI AS
ROLE OF ENDOGENOUS GAMMA-INTERFERON IN HOST RESPONSE TO INFECTION WITH BLOOD-STAGE PLASMODIUM-CHABAUDI AS
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DOI：
10.1128/iai.58.10.3225-3232.1990
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发表时间：
1990-10-01
影响因子：
3.1
通讯作者：
PODOBA, JE
中科院分区：
文献类型：
--
作者：
STEVENSON, MM;TAM, MF;PODOBA, JE
γ干扰素（IFN-. γ）是一种能够激活巨噬细胞的多能淋巴因子，在获得性免疫中对血期疟疾的作用进行了研究。c57bl来源的脂多糖抗性C57BL-10ScN小鼠对106个寄生于chabaudi AS的红细胞腹腔感染具有抗性，用单克隆抗ifn -. γ治疗。抗体(MAb)。使用两种单克隆抗体：R4-6A2，一种大鼠抗小鼠，中和免疫球蛋白G1，它是针对天然小鼠IFN-. γ制备的。DB-1是一种针对重组大鼠IFN- γ制备的小鼠抗大鼠免疫球蛋白G1。，可以中和老鼠分子和老鼠分子。C57BL/10ScNH小鼠腹腔注射200 .mu。R4-6A2感染前1天及每3天至第21天注射一次。对照组小鼠用正常大鼠血清处理。在单独的实验中，从感染当天开始，给药DB-1（每周1.0 mg，连续4周）；对照组小鼠未经治疗。对照组和单抗组小鼠腹腔感染106个寄生的红血球，观察感染的过程和结果。对照小鼠表现出一个感染过程，其特征是寄生红细胞在30%至40%之间达到高峰，并在4周内消除寄生虫。单抗处理小鼠在寄生高峰前1 ~ 2天表现出明显较高的寄生高峰，且在4周内完全清除感染。因此，这些结果提示抗ifn - γ治疗。MAb削弱但不完全消除宿主对chabaudi AS的抗性。我们还检查了IFN- γ的动力学。用疟疾抗原或豆豆蛋白a体外培养的脾细胞产生疟原虫，在腹腔感染106个寄生红细胞后，在不同时间恢复C57BL/6小鼠的脾细胞。IFN-。γ的量。酶联免疫吸附法定量。在每种情况下，IFN-。产生发生在寄生高峰之前，随后减少到很少或没有IFN- γ。感染后42天的产量。因此，在产生IFN- γ的动力学之间存在相似之处。体外通过感染动物的脾细胞和体内对内源性分子的需求，在寄生虫病高峰期之前和时候。总之，这些结果表明IFN-。寄主对chabaudi AS的抗性有依赖和不依赖机制。
The role of gamma interferon (IFN-.gamma.), a pluripotent lymphokine capable of activating macrophages, in acquired immunity to blood-stage malaria was investigated. C57BL-derived, lipopolysaccharride-resistant C57BL-10ScN mice, which were found to be resistant to intraperitoneal (i.p.) infection with 106 Plasmodium chabaudi AS parasitized erythrocytes, were treated with monoclonal anti-IFN-.gamma. antibody (MAb). Two MAbs were used: R4-6A2, a rat anti-mouse, neutralizing immunoglobulin G1, which was prepared against natural murine IFN-.gamma., and DB-1, a murine anti-rat immunoglobulin G1 prepared against recombinant rat IFN-.gamma., which can neutralize the murine molecule as well as the rat molecule. C57BL/10ScNH mice were injected i.p. with 200 .mu.g of R4-6A2 1 day before infection and every 3 days through day 21. Control mice were treated with normal rat serum. In separate experiments, DB-1 (1.0 mg per week for 4 weeks) was administered i.p. to C57BL/10ScNH mice beginning on the day of infection; control mice were untreated. Control and MAb-treated mice were infected i.p. with 106 P. chabaudi AS parasitized erythrocytes, and the course and outcome of infection were determined. Control mice exhibited a course of infection that was characterized by a peak prarasitemia between 30 and 40% parasitized erythrocytes and elimination of the parasite by 4 weeks. MAb-treated mice exhibited a significantly greater parasitemia 1 to 2 days before the peak parasitemia as well as a significantly greater peak parasitemia but also completely cleared the infection by 4 weeks. Thus, these results suggest that treatment with anti-IFN-.gamma. MAb impairs but does not completely abrogate host resistance to P. chabaudi AS. We also examined the kinetics of IFN-.gamma. production by spleen cells cultured in vitro with malaria antigen or concanavalin A. Spleen cells were recovered from individual C57BL/6 mice at various times after i.p. infection with 106 P. chabaudi AS parasitized erythrocytes. The amount of IFN-.gamma. produced was quantitated by enzyme-linked immunosorbent assay. In each case, the peak of IFN-.gamma. production occurred just before the peak parasitemia, followed by a decrease to little or no IFN-.gamma. production through 42 days postinfection. There was thus a parallel between the kinetics of production of IFN-.gamma. in vitro by spleen cells from infected animals and the requirement in vivo for the endogenous molecule just before and at the time of peak parasitemia. In conclusion, these results suggest that IFN-.gamma.-dependent and -independent mechanisms contribute to host resistance to P. chabaudi AS.