Kaleab B, Ottenoff T, Converse P, Halapi E, Tadesse G, Rottenberg M, Kiessling R
Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
Eur J Immunol. 1990 Dec;20(12):2651-9. doi: 10.1002/eji.1830201219.
Little information is available about the generation and specificity of the cytotoxic cells that eliminate human monocytes/macrophages infected with mycobacteria. To address this we have developed a cytotoxicity assay in which 51Cr-labeled monocytes pulsed with bacillus Calmette Guerin (BCG) or Mycobacterium leprae, were used as target cells in overnight cytotoxicity assays. As effector cells, peripheral blood mononuclear cells from healthy occupational contacts or from leprosy patients stimulated with antigen for 7 days were used. Cytotoxicity against antigen-pulsed monocytes that could be induced by mycobacterial antigens was proportional to the degree of antigen responsiveness in each individual, as measured in lymphocyte transformation tests. The lepromatous leprosy patients tested were often poor responders to BCG as well as M. leprae, both with regard to induction of cytotoxicity as well as in lympho-proliferation. Killing was significantly higher against antigen-pulsed vs. nonpulsed monocytes, although significant killing was induced against the latter as well and paralleled by induction of natural killer activity against the K-562 target cell. Cross-reactivity was observed between BCG and M. leprae, but not with unrelated antigen (tetanus toxoid) or with endogenous stress proteins induced by heat shock. M. leprae- and BCG-activated cytotoxic cells were found in both the CD4-CD8+ and CD4+CD8- populations, whereas in contrast the soluble antigen, purified protein derivative of M. tuberculosis, generated cytotoxic cells that were exclusively of the CD4+ phenotype. The involvement of both specific T cells as well as nonspecific cells in the killing of human macrophages may be important with respect to protection and immunopathology induced by mycobacterial antigens.
关于清除感染分枝杆菌的人类单核细胞/巨噬细胞的细胞毒性细胞的产生和特异性，目前所知甚少。为了解决这个问题，我们开发了一种细胞毒性测定方法，其中用卡介苗（BCG）或麻风分枝杆菌脉冲标记的51Cr单核细胞作为过夜细胞毒性测定的靶细胞。作为效应细胞，使用来自健康职业接触者或用抗原刺激7天的麻风病人的外周血单核细胞。针对可由分枝杆菌抗原诱导的抗原脉冲单核细胞的细胞毒性与每个个体在淋巴细胞转化试验中测得的抗原反应程度成正比。所测试的瘤型麻风病人通常对卡介苗和麻风分枝杆菌的反应都很差，无论是在细胞毒性诱导还是淋巴细胞增殖方面。与未脉冲抗原的单核细胞相比，对抗原脉冲单核细胞的杀伤作用明显更高，尽管对后者也有明显的杀伤作用，并且与针对K-562靶细胞的自然杀伤活性的诱导平行。在卡介苗和麻风分枝杆菌之间观察到交叉反应，但与无关抗原（破伤风类毒素）或热休克诱导的内源性应激蛋白没有交叉反应。在CD4-CD8+和CD4+CD8-群体中都发现了麻风分枝杆菌和卡介苗激活的细胞毒性细胞，而相比之下，结核分枝杆菌的可溶性抗原纯化蛋白衍生物产生的细胞毒性细胞仅为CD4+表型。特异性T细胞和非特异性细胞在人类巨噬细胞杀伤中的参与对于分枝杆菌抗原诱导的保护和免疫病理学可能很重要。
