Essential Requirement of Antigen Presentation by Monocyte Lineage Cells for the Activation of Primary Human γδ T Cells by Aminobisphosphonate Antigen

Human gammadelta T cells respond to nonpeptide Ags such as pyrophosphomonoesters and alkylamines in a gammadelta TCR-dependent manner in the absence of other APCS: Recently, aminobisphosphonates such as pamidronate have also been shown to activate human gammadelta T cells. In the present study, we indicate that activation of primary gammadelta T cells by pamidronate strictly depends on the presence of monocyte-lineage cells, unlike that by pyrophosphomonoesters. Thus, although pamidronate induced cell clustering, proliferation, and IFN-gamma production of gammadelta T cells in the culture of PBMC, it failed to induce any of these activities in the culture of purified primary gammadelta T cells. By adding back the purified monocytes, however, both cell clustering and IFN-gamma production of gammadelta T cells by pamidronate could be restored. The pamidronate-pulsed, but not untreated, myelomonocytic line, THP-1, was capable of activating the purified gammadelta T cells to produce IFN-gamma, which was associated with the down-regulation of gammadelta TCR. Furthermore, pamidronate-pulsed THP-1 cells were significantly more susceptible to gammadelta T cell-mediated cytotoxicity than untreated THP-1. Also, TCR-defective Jurkat T cells transfected with gammadelta 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 gammadelta T cells are functionally activated via gammadelta TCR by aminobisphosphonate Ag presented on the surface of monocyte lineage cells rather than directly by its free form.