Carvalho E M, Bacellar O, Brownell C, Regis T, Coffman R L, Reed S G
Immunology Service of University Hospital Professor Edgard Santos, Federal University of Bahia, Salvador-Bahia, Brazil.
J Immunol. 1994 Jun 15;152(12):5949-56.
Visceral leishmaniasis is associated with a marked depression of T cell responses, which has been characterized by the absence of IL-2 and IFN-gamma production by lymphocytes on in vitro stimulation with Leishmania Ag. The aim of this study was to evaluate both the mechanism of these immunologic abnormalities and the restoration of in vitro T cell responses to Leishmania Ags. A total of 15 untreated visceral leishmaniasis patients were evaluated. Although IFN-gamma and IL-4 levels in the supernatants of lymphocyte cultures were very low or absent, mRNA for these cytokines and for IL-10 were observed in PBMCs. Addition of IFN-gamma plus IL-2 enhanced lymphocyte proliferation by 158%. Restoration of T cell proliferative responses and IFN-gamma production was also observed by the addition of a neutralizing mAb alpha-IL-10. Neutralizing mAb alpha-IL-4 did not restore T cell responses but alpha-IL-10 and alpha-IL-4 mAbs had a synergistic effect on lymphocyte proliferation. The IFN-gamma levels in supernatants of lymphocyte cultures stimulated with Leishmania chagasi Ag or L. chagasi Ag plus alpha-IL-4, alpha-IL-10, or alpha-IL-4 plus alpha-IL-10 mAbs were 26 +/- 30 pg/ml, 41 +/- 18 pg/ml, 146 +/- 73 pg/ml, and 174 +/- 106 pg/ml, respectively. These data indicate that Th2 cell activation occurs in visceral leishmaniasis and that in vitro production of IFN-gamma and lymphocyte proliferation can be restored by blocking the inhibitory effect of the Th2 cytokines on mononuclear cells.
内脏利什曼病与T细胞反应的显著抑制有关，其特征是淋巴细胞在体外受利什曼原虫抗原刺激时不产生白细胞介素-2（IL-2）和γ干扰素（IFN-γ）。本研究的目的是评估这些免疫异常的机制以及体外T细胞对利什曼原虫抗原反应的恢复情况。共评估了15例未经治疗的内脏利什曼病患者。尽管淋巴细胞培养上清液中的IFN-γ和IL-4水平非常低或检测不到，但在外周血单核细胞（PBMCs）中观察到了这些细胞因子以及IL-10的信使核糖核酸（mRNA）。添加IFN-γ加IL-2可使淋巴细胞增殖提高158%。添加中和性单克隆抗体α-IL-10也观察到T细胞增殖反应和IFN-γ产生的恢复。中和性单克隆抗体α-IL-4不能恢复T细胞反应，但α-IL-10和α-IL-4单克隆抗体对淋巴细胞增殖有协同作用。用恰加斯利什曼原虫抗原或恰加斯利什曼原虫抗原加α-IL-4、α-IL-10或α-IL-4加α-IL-10单克隆抗体刺激的淋巴细胞培养上清液中的IFN-γ水平分别为26±30皮克/毫升、41±18皮克/毫升、146±7皮克/毫升和174±106皮克/毫升。这些数据表明，在内脏利什曼病中发生了辅助性T细胞2（Th2）细胞活化，并且通过阻断Th2细胞因子对单核细胞的抑制作用，可以恢复体外IFN-γ的产生和淋巴细胞增殖。
