Essential requirement of antigen presentation by monocyte lineage cells for the activation of primary human γδ T cells by aminobisphosphonate antigen
Essential requirement of antigen presentation by monocyte lineage cells for the activation of primary human γδ T cells by aminobisphosphonate antigen
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DOI：
10.4049/jimmunol.166.9.5508
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发表时间：
2001-05-01
影响因子：
4.4
通讯作者：
Minato, N
中科院分区：
文献类型：
--
作者：
Miyagawa, F;Tanaka, Y;Minato, N
在缺乏其他APC的情况下，人的Gamma Delta T细胞对焦磷酸单酯和烷基胺等非肽AGS的反应依赖于Gamma Delta TCR。最近，氨基二膦酸盐，如帕米膦酸盐，也被证明可以激活人的伽马三角洲T细胞。在目前的研究中，我们指出，帕米磷酸钠对初级伽马三角洲T细胞的激活严格依赖于单核细胞细小细胞的存在，而不是焦磷酸单酯。因此，尽管帕米磷酸钠在PBMC培养中诱导细胞聚集、增殖和产生干扰素-γ，但在纯化的原代γ-增量T细胞培养中不能诱导任何这些活性。然而，通过重新加入纯化的单核细胞，帕米磷酸酯可以恢复细胞聚集和帕米磷酸钠产生的干扰素-γ。帕米磷酸钠冲击但不是未经处理的骨髓单核细胞系THP-1能够激活纯化的Gamma Delta T细胞产生干扰素-Gamma，这与Gamma Delta TCR下调有关。此外，帕米磷酸钠冲击的THP-1细胞比未经处理的THP-1细胞更容易受到伽马增量T细胞介导的细胞毒作用的影响。此外，TCR基因缺陷的Jurkat T细胞在帕米磷酸钠冲击的THP-1细胞中产生了显著水平的IL-2。这些结果有力地表明，人的Gamma Delta T细胞是通过Gamma Delta TCR被存在于单核细胞系细胞表面的氨基双膦酸银激活的，而不是直接通过其游离形式激活的。
Human gamma delta T cells respond to nonpeptide Ags such as pyrophosphomonoesters and alkylamines in a gamma delta TCR-dependent manner in the absence of other APCs. Recently, aminobisphosphonates such as pamidronate have also been shown to activate human gamma delta T cells. In the present study, we indicate that activation of primary gamma delta T cells by pamidronate strictly depends on the presence of monocyte-fineage cells, unlike that by pyrophosphomonoesters. Thus, although pamidronate induced cell clustering, proliferation, and IFN-gamma production of gamma delta T cells in the culture of PBMC, it failed to induce any of these activities in the culture of purified primary gamma delta T cells. By adding back the purified monocytes, however, both cell clustering and IFN-gamma production of gamma delta T cells by pamidronate could be restored. The pamidronate-pulsed, but not untreated, myelomonocytic line, THP-1, was capable of activating the purified gamma delta T cells to produce IFN-gamma, which was associated with the down-regulation of gamma delta TCR. Furthermore, pamidronate-pulsed THP-1 cells were significantly more susceptible to gamma delta T cell-mediated cytotoxicity than untreated THP-1. Also, TCR-defective Jurkat T cells transfected with gamma delta TCR genes produced a significant level of IL-2 in response to the pamidronate-pulsed THP-1 cells. These results have suggested strongly that human gamma delta T cells are functionally activated via gamma delta TCR by aminobisphosphonate Ag presented on the surface of monocyte lineage cells rather than directly by its free form.