Barral A, Teixeira M, Reis P, Vinhas V, Costa J, Lessa H, Bittencourt A L, Reed S, Carvalho E M, Barral-Netto M
Faculdade de Medicina, Serviço de Imunologia, Universidade Federal da Bahia, Salvador-Bahia, Brazil.
Am J Pathol. 1995 Oct;147(4):947-54.
Transforming growth factor (TGF)-beta has several downregulatory functions on the immune system: inhibition of interleukin-2 receptor induction, decrease of interferon-gamma-induced class II antigen expression, inhibition of macrophage activation, as well as cytotoxic and lymphokine-activated killer cell generation. TGF-beta has also been recognized as an important immunoregulator in murine leishmaniasis, for which it increases susceptibility to disease. In the present study we evaluate the involvement of TGF-beta in human leishmaniasis in vitro and in patients with cutaneous leishmaniasis. Human macrophages produce active TGF-beta after infection by Leishmania amazonensis (480 +/- 44.7 pg/ml; mean +/- SEM), L. donovani chagasi (295 +/- 7.6 pg/ml), or L. braziliensis (196 +/- 15.7 pg/ml). When TGF-beta was added to cultures of human macrophages infected with L. braziliensis it led to an increase of approximately 50% in parasite numbers as compared with untreated cultures. Exogenous TGF-beta added to macrophage cultures was able to reverse the effect of interferon-gamma in controlling Leishmania growth. Even at 100 IU/ml interferon-gamma the presence of TGF-beta increases the number of intracellular parasites. On the other hand, TNF-alpha at high concentration (100 IU/ml) totally blunts the suppressive effect of TGF-beta. Immunostaining for TGF-beta was observed in the dermis, produced by fibroblasts and occasionally by inflammatory cells in the biopsies from human leishmaniasis lesions, being present in most of the biopsies taken from patients with early cutaneous leishmaniasis (less than 2 months of ulcer development) and in cases of active mucosal leishmaniasis. Taken together these observations suggest an important role for TGF-beta in human leishmaniasis, with its production by infected macrophages being probably related to parasite establishment in the early stages of the disease.
转化生长因子（TGF）-β对免疫系统具有多种下调功能：抑制白细胞介素-2受体诱导、降低干扰素-γ诱导的II类抗原表达、抑制巨噬细胞活化以及细胞毒性和淋巴因子激活的杀伤细胞生成。TGF-β也被认为是小鼠利什曼病中的一种重要免疫调节因子，它会增加对该病的易感性。在本研究中，我们评估了TGF-β在体外人类利什曼病以及皮肤利什曼病患者中的作用。人类巨噬细胞在被亚马逊利什曼原虫（480±44.7 pg/ml；平均值±标准误）、杜氏利什曼原虫恰加斯亚种（295±7.6 pg/ml）或巴西利什曼原虫（196±15.7 pg/ml）感染后会产生活性TGF-β。当将TGF-β添加到感染巴西利什曼原虫的人类巨噬细胞培养物中时，与未处理的培养物相比，寄生虫数量增加了约50%。添加到巨噬细胞培养物中的外源性TGF-β能够逆转干扰素-γ在控制利什曼原虫生长方面的作用。即使在100 IU/ml的干扰素-γ存在下，TGF-β的存在也会增加细胞内寄生虫的数量。另一方面，高浓度（100 IU/ml）的肿瘤坏死因子-α完全消除了TGF-β的抑制作用。在人类利什曼病病变活检中，在真皮中观察到TGF-β的免疫染色，由成纤维细胞产生，偶尔也由炎症细胞产生，在大多数来自早期皮肤利什曼病（溃疡发展少于2个月）患者的活检以及活动性黏膜利什曼病病例中都存在。综上所述，这些观察结果表明TGF-β在人类利什曼病中起重要作用，感染的巨噬细胞产生TGF-β可能与疾病早期阶段寄生虫的定植有关。
