Ueta C, Kawasumi H, Fujiwara H, Miyagawa T, Kida H, Ohmoto Y, Kishimoto S, Tsuyuguchi I
Osaka Prefectural Habikino Hospital, Japan.
Eur J Immunol. 1996 Dec;26(12):3066-73. doi: 10.1002/eji.1830261237.
gammadelta T cell populations are known to expand in response to intracellular bacterial infectious agents regardless of previous priming. We have shown previously that soluble factor(s) produced by Mycobacterium-stimulated monocytes activate cord blood gammadelta T cells to proliferate. In this study, we investigated whether cytokines produced by monocytes are responsible for gammadelta T cell activation in vitro: interleukin (IL)-1beta, IL-6, IL-8, IL-12, tumor necrosis factor (TNF)-alpha and granulocyte/macrophage colony-stimulating factor were examined. Recombinant human IL-12 stimulated gammadelta T cells, but not alphabeta T cells in peripheral blood mononuclear cells, to express CD25 on their surfaces, and to expand in number in vitro. IL-12-primed gammadelta T cell numbers increased to a greater extent in the culture to which exogenous IL-2 (5 U/ml) was added. Anti-TNF-alpha monoclonal antibody inhibited IL-12-induced up-regulation of CD25 on gammadelta T cells, suggesting that endogenous TNF-alpha may play a role in IL-12-induced activation of gammadelta T cells. Recombinant TNF-alpha synergistically augmented IL-12-induced activation of gammadelta T cells. Furthermore, IL-12 up-regulated TNF receptors on gammadelta T cells in vitro: TNF-alpha binding to its receptor induced CD25 expression on the gammadelta T cells in an autocrine or paracrine fashion, or perhaps both. It also became evident that both IL-12 and TNF-alpha were produced by mycobacterial lysate-stimulated monocytes. Taken together, these results suggest that upon confrontation with mycobacterial organisms, gammadelta T cells can be quickly and antigen-nonspecifically activated by soluble factors including IL-12 and TNF-alpha, both of which are produced by mononuclear phagocytes in response to mycobacterial organisms.
已知γδT细胞群体可响应细胞内细菌感染因子而扩增，无论之前是否接触过抗原。我们之前已表明，经分枝杆菌刺激的单核细胞产生的可溶性因子可激活脐血γδT细胞增殖。在本研究中，我们调查了单核细胞产生的细胞因子是否在体外负责γδT细胞的激活：检测了白细胞介素（IL）-1β、IL-6、IL-8、IL-12、肿瘤坏死因子（TNF）-α和粒细胞/巨噬细胞集落刺激因子。重组人IL-12刺激外周血单个核细胞中的γδT细胞而非αβT细胞在其表面表达CD25，并在体外扩增。在添加外源性IL-2（5 U/ml）的培养物中，经IL-12预处理的γδT细胞数量增加得更多。抗TNF-α单克隆抗体抑制IL-12诱导的γδT细胞上CD25的上调，表明内源性TNF-α可能在IL-12诱导的γδT细胞激活中起作用。重组TNF-α协同增强IL-12诱导的γδT细胞激活。此外，IL-12在体外上调γδT细胞上的TNF受体：TNF-α与其受体结合以自分泌或旁分泌方式，或可能两者兼具，诱导γδT细胞上CD25的表达。还明显看出，经分枝杆菌裂解物刺激的单核细胞会产生IL-12和TNF-α。综上所述，这些结果表明，在与分枝杆菌接触时，γδT细胞可被包括IL-12和TNF-α在内的可溶性因子快速且非特异性地激活，这两种因子均由单核吞噬细胞响应分枝杆菌而产生。
