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T Cells by Aminobisphosphonate Antigen1
Department of Immunology and Cell Biology, Graduate School of Biostudies and Graduate School of Medicine, Kyoto University, Kyoto, Japan
Human 
T cells respond to nonpeptide Ags such as
pyrophosphomonoesters and alkylamines in a TCR-dependent manner
in the absence of other APCs. Recently, aminobisphosphonates such as
pamidronate have also been shown to activate human T cells. In
the present study, we indicate that activation of primary 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- production of T cells in the culture of PBMC, it failed
to induce any of these activities in the culture of purified primary
T cells. By adding back the purified monocytes, however, both
cell clustering and IFN- production of T cells by pamidronate
could be restored. The pamidronate-pulsed, but not untreated,
myelomonocytic line, THP-1, was capable of activating the purified
T cells to produce IFN-, which was associated with the
down-regulation of TCR. Furthermore, pamidronate-pulsed THP-1
cells were significantly more susceptible to T cell-mediated
cytotoxicity than untreated THP-1. Also, TCR-defective Jurkat T cells
transfected with 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 T cells are functionally activated
via TCR by aminobisphosphonate Ag presented on the surface of
monocyte lineage cells rather than directly by its free form
.
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