de la Barrera S, Finiasz D M, Fink S, Valdez R, Bottasso O, Balina L M, Sasiain M C
Departamento Inmunologia, Instituto de Investigaciones Hematologicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
Int J Lepr Other Mycobact Dis. 1997 Mar;65(1):45-55.
In the present study we evaluated the contribution of CD4 and CD8 T cells on the antigen-specific cytotoxic activity induced by whole Mycobacterium leprae in leprosy patients and normal controls (N) as well as the modulation of this activity by some cytokines. Peripheral blood mononuclear cells (PBMC) from N or from leprosy patients were stimulated with antigen in the presence or absence of cytokines for 7 days. M. leprae-stimulated PBMC were depleted of CD4 or CD8 antigen-bearing cells and employed as effector cells in a 4-hr [31Cr]-release assay against autologous M. leprae-pulsed macrophages. Our results demonstrate that both CD4 and CD8 T cells contribute to M. leprae-induced cytotoxic activity, with differences observed in paucibacillary (PB) and multibacillary (MB) patients. CD8-mediated cytotoxic activity is higher than that of CD4 cells in PB patients, while in MB patients CD4 cytotoxicity is predominant. Our data also demonstrate that the generation of CD4 and CD8 cytotoxic T lymphocytes (CTL) can be modulated differentially by interleukin-4 (IL-4), IL-6, gamma interferon (IFN-gamma), or IL-2. Although MB patients developed the lowest CTL response, cytokines such as IL-6 plus IL-2 or IFN-gamma were able to generate both CD4 and CD8 cytotoxic T cells from MB patients. In PB patients, IL-6 plus IFN-gamma displayed the highest stimulation on CD8 effector cells. Thus, an important role may be assigned to IL-6, together with IL-2 or IFN-gamma, in the differentiation of M. leprae-specific CTL effector cells.
在本研究中，我们评估了CD4和CD8 T细胞对麻风患者和正常对照（N）中由完整麻风分枝杆菌诱导的抗原特异性细胞毒性活性的贡献，以及某些细胞因子对该活性的调节作用。来自N或麻风患者的外周血单个核细胞（PBMC）在有或无细胞因子存在的情况下用抗原刺激7天。用抗CD4或抗CD8抗体去除麻风分枝杆菌刺激的PBMC中携带相应抗原的细胞，并将其用作效应细胞，在4小时的[31Cr]释放试验中作用于自体麻风分枝杆菌脉冲巨噬细胞。我们的结果表明，CD4和CD8 T细胞均对麻风分枝杆菌诱导的细胞毒性活性有贡献，在少菌型（PB）和多菌型（MB）患者中观察到差异。在PB患者中，CD8介导 的细胞毒性活性高于CD4细胞，而在MB患者中，CD4细胞毒性占主导。我们的数据还表明，白细胞介素-4（IL-4）、IL-6、γ干扰素（IFN-γ）或IL-2可以不同程度地调节CD4和CD8细胞毒性T淋巴细胞（CTL）的产生。尽管MB患者产生的CTL反应最低，但IL-6加IL-2或IFN-γ等细胞因子能够从MB患者中产生CD4和CD8细胞毒性T细胞。在PB患者中，IL-6加IFN-γ对CD8效应细胞的刺激作用最强。因此，IL-6与IL-2或IFN-γ一起在麻风分枝杆菌特异性CTL效应细胞的分化中可能起着重要作用。
