Essential requirement of antigen presentation by monocyte lineage cells for the activation of primary human gamma delta 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.
Miyagawa
F
F
Department of Immunology and Cell Biology, Graduate School of Biostudies and Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Tanaka
Y
Y
Yamashita
S
S
Minato
N
N
D017951:Antigen Presentation / Q000187:drug effects / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D000941:Antigens / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002449:Cell Aggregation / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004164:Diphosphonates / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D010755:Organophosphates / Q000494:pharmacology; D000077268:Pamidronate; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000941:Antigens; D004164:Diphosphonates; D010755:Organophosphates; D016692:Receptors, Antigen, T-Cell, gamma-delta; C088826:monoethyl phosphate; D000077268:Pamidronate