Gabaglia C R, Valle M T, Fenoglio D, Barcinski M A, Manca F
Immunology Laboratory-University of Genoa, San Martino Hospital, Genoa, Italy.
Hum Immunol. 2000 Jun;61(6):531-7. doi: 10.1016/s0198-8859(00)00119-1.
T cell mediated immunity is known to play a central role in the host response to control intra-cellular pathogens. This work demonstrates the presence of specific CD4(+) T cells to Leishmania spp. antigens in peripheral mononuclear cells of naïve individuals (normal volunteers from non-endemic regions). The responder population was expanded by generation of antigen-specific T cell lines, which were produced by repeated stimulation with fixed promastigotes and autologous irradiated PBMC as antigen presenting cells. The leishmania-T cell lines were shown to proliferate in response to different species of the parasite (L. amazonensis, L. braziliensis, and L. donovani), but not to other recall antigens such as Candida albicans or tetanus toxoid. A preferential expansion of IFNgamma and IL-2 producing Th1-like T cells was observed. The leishmania-reactive cells were distributed between CD4(+) CD45RA(+) ("naïve") and CD4(+) CD45R0(+) ("memory") populations. Although limiting dilution analysis showed a precursor frequency 3 times lower within the naïve compartment, similar numbers of T cell lines were derived from both purified subpopulations. This study using leishmania-specific CD4(+) T cell lines produced from normal individuals should provide information on cellular immune responses that are triggered by the parasite and how infection impacts the naïve T cell repertoire.
已知T细胞介导的免疫在宿主控制细胞内病原体的反应中起核心作用。这项研究证明了在未接触过病原体的个体(来自非流行地区的正常志愿者)的外周血单核细胞中存在针对利什曼原虫属抗原的特异性CD4(+) T细胞。通过产生抗原特异性T细胞系来扩增应答细胞群体,该细胞系是通过用固定前鞭毛体和作为抗原呈递细胞的自体照射外周血单核细胞反复刺激而产生的。利什曼原虫-T细胞系被证明能对不同种类的寄生虫(亚马逊利什曼原虫、巴西利什曼原虫和杜氏利什曼原虫)产生增殖反应,但对其他回忆抗原如白色念珠菌或破伤风类毒素无反应。观察到产生IFNγ和IL-2的Th1样T细胞优先扩增。利什曼原虫反应性细胞分布在CD4(+) CD45RA(+)(“初始”)和CD4(+) CD45R0(+)(“记忆”)群体之间。尽管有限稀释分析显示初始亚群中的前体细胞频率低3倍,但从两个纯化亚群中获得的T细胞系数量相似。这项使用从正常个体产生的利什曼原虫特异性CD4(+) T细胞系的研究应能提供有关寄生虫引发的细胞免疫反应以及感染如何影响初始T细胞库的信息。