Boom W H, Chervenak K A, Mincek M A, Ellner J J
Division of Infectious Diseases, School of Medicine, Case Western Reserve University, and Cleveland, Ohio.
Infect Immun. 1992 Sep;60(9):3480-8. doi: 10.1128/iai.60.9.3480-3488.1992.
gamma delta T cells, both human and murine, have been found to be highly responsive to mycobacterial antigens. However, the role and function of gamma delta T cells in the immune response to Mycobacterium tuberculosis remain largely unknown. In earlier studies, we demonstrated that monocytes infected with live M. tuberculosis were particularly effective inducers of human peripheral blood gamma delta T cells. The present studies were performed to further characterize the interaction between human mononuclear phagocytes, gamma delta T cells, and live M. tuberculosis, in comparison with CD4+ T cells. First, we found that resting gamma delta T cells expanded in vitro by live M. tuberculosis were specific for M. tuberculosis, and that heat killing and washing the mycobacteria removed the antigen(s) for gamma delta T cells. In contrast, the heat-killed mycobacteria retained significant antigenicity for CD4+ T cells. Second, live M. tuberculosis-expanded gamma delta T cells from healthy tuberculin-positive donors did not respond significantly to the antigens in M. tuberculosis culture filtrate, including the 65- and 71-kDa mycobacterial heat shock proteins. Third, the activation of gamma delta T cells by live mycobacteria was dependent on antigen-presenting cells, and mononuclear phagocytes were found to be very efficient antigen-presenting cells both for resting peripheral blood gamma delta T cells and for activated expanded gamma delta T cells. The mononuclear phagocyte carried the necessary costimulatory factors necessary for gamma delta T-cell proliferation. Fourth, the antigen repertoire and HLA requirements for CD4+ memory T cells and those for gamma delta T cells appear to be quite distinct from each other. CD4+ T cells recognized both soluble protein antigens and whole organisms in a class II major histocompatibility complex-restricted manner, whereas gamma delta T cells appeared to recognize only constituents associated with the whole organism and were not restricted by class I or class II major histocompatibility complex molecules. Finally, the assay system described to expand and purify responding CD4+ and gamma delta T cells after stimulation with live M. tuberculosis represented a simple approach to the direct comparison of these two T-cell populations in the interaction with mononuclear phagocytes infected with M. tuberculosis. Such studies provide insight not only into the relative roles of human CD4+ and gamma delta T cells in the human immune response to intracellular bacterial pathogens such as M. tuberculosis but also into the basic biologic role of human gamma delta T cells in antimicrobial immunity.
已发现人类和小鼠的γδT细胞对分枝杆菌抗原具有高度反应性。然而，γδT细胞在针对结核分枝杆菌的免疫反应中的作用和功能仍 largely未知。在早期研究中，我们证明感染活结核分枝杆菌的单核细胞是人类外周血γδT细胞的特别有效的诱导剂。进行本研究是为了进一步表征人类单核吞噬细胞、γδT细胞和活结核分枝杆菌之间的相互作用，并与CD4+T细胞进行比较。首先，我们发现活结核分枝杆菌在体外扩增的静息γδT细胞对结核分枝杆菌具有特异性，并且热灭活和洗涤分枝杆菌会去除γδT细胞的抗原。相比之下，热灭活的分枝杆菌对CD4+T细胞保留了显著的抗原性。其次，来自健康结核菌素阳性供体的活结核分枝杆菌扩增的γδT细胞对结核分枝杆菌培养滤液中的抗原，包括65 kDa和71 kDa的分枝杆菌热休克蛋白，没有明显反应。第三，活分枝杆菌对γδT细胞的激活依赖于抗原呈递细胞，并且发现单核吞噬细胞对于静息外周血γδT细胞和活化扩增的γδT细胞都是非常有效的抗原呈递细胞。单核吞噬细胞携带γδT细胞增殖所需的必要共刺激因子。第四，CD4+记忆T细胞和γδT细胞的抗原库和HLA要求似乎彼此相当不同。CD4+T细胞以II类主要组织相容性复合体限制的方式识别可溶性蛋白质抗原和整个生物体，而γδT细胞似乎仅识别与整个生物体相关的成分，并且不受I类或II类主要组织相容性复合体分子的限制。最后，所述用于在活结核分枝杆菌刺激后扩增和纯化反应性CD4+和γδT细胞的测定系统代表了一种简单的方法，用于直接比较这两个T细胞群体在与感染结核分枝杆菌的单核吞噬细胞相互作用中的情况。此类研究不仅有助于深入了解人类CD4+和γδT细胞在人类针对细胞内细菌病原体如结核分枝杆菌的免疫反应中的相对作用，还有助于深入了解人类γδT细胞在抗菌免疫中的基本生物学作用。
