Rodrigues V, Santana da Silva J, Campos-Neto A
Immunology Laboratory, Medical School of Triângulo Mineiro, Uberaba, MG, Brazil.
Infect Immun. 1998 Mar;66(3):1233-6. doi: 10.1128/IAI.66.3.1233-1236.1998.
Hamsters infected with Leishmania donovani develop a disease similar to human kala-azar. They present hypergammaglobulinemia, and their T cells do not respond to parasite antigens. This unresponsiveness has been primarily ascribed to defects in antigen-presenting cells (APCs), because these cells are unable to stimulate proliferation of parasite-specific T cells from immunized animals. In this study, we show that APCs (adherent spleen cells) from L. donovani-infected hamsters produce high levels of the inhibitory cytokine transforming growth factor beta (TGF-beta). Immunohistochemical studies with an anti-TGF-beta monoclonal antibody (MAb) showed that this cytokine is abundantly produced in vivo by the spleen cells of infected animals. In addition, high levels of TGF-beta are produced in vitro by infected hamster cells, either spontaneously or after stimulation with parasite antigen or lipopolysaccharide. Furthermore, in vivo-infected adherent cells obtained from spleens of L. donovani-infected hamsters caused profound inhibition of the in vitro antigen-induced proliferative response of lymph node cells from hamsters immunized with leishmanial antigens. Moreover, this inhibition was totally abrogated by the anti-TGF-beta MAb. These results suggest that the immunosuppression observed in visceral leishmaniasis is, at least in part, due to the abundant production of TGF-beta during the course of the infection.
感染杜氏利什曼原虫的仓鼠会患上一种类似于人类黑热病的疾病。它们出现高球蛋白血症，其T细胞对寄生虫抗原无反应。这种无反应性主要归因于抗原呈递细胞（APC）的缺陷，因为这些细胞无法刺激来自免疫动物的寄生虫特异性T细胞增殖。在本研究中，我们发现来自感染杜氏利什曼原虫的仓鼠的APC（贴壁脾细胞）产生高水平的抑制性细胞因子转化生长因子β（TGF-β）。用抗TGF-β单克隆抗体（MAb）进行的免疫组织化学研究表明，这种细胞因子在感染动物的脾细胞中在体内大量产生。此外，感染的仓鼠细胞在体外自发地或在用寄生虫抗原或脂多糖刺激后产生高水平的TGF-β。此外，从感染杜氏利什曼原虫的仓鼠脾脏中获得的体内感染的贴壁细胞对用利什曼原虫抗原免疫的仓鼠的淋巴结细胞的体外抗原诱导的增殖反应产生了显著抑制。而且，这种抑制被抗TGF-β MAb完全消除。这些结果表明，在内脏利什曼病中观察到的免疫抑制至少部分是由于感染过程中TGF-β的大量产生。
