Reciprocal activating interaction between dendritic cells and pamidronate-stimulated gammadelta T cells: role of CD86 and inflammatory cytokines.
We investigated the interactions between human monocyte-derived dendritic cells (DCs) and Ag-activated circulating TCR-gammadelta-expressing lymphocytes (Vdelta2). Coculture of immature DCs (iDCs) with peripheral blood Vdelta2 T cells activated with either pyrophosphomonoesters (isopentenyl pyrophosphate; IPP) or aminobiphosphonates (pamidronate; PAM) led to a significant up-modulation of CD86 and MHC class I molecules and to the acquisition of functional features typical of activated DCs. DC activation induced by both IPP- and PAM-stimulated gammadelta T cells was mostly mediated by TNF-alpha and IFN-gamma secreted by activated lymphocytes. However, the effect of PAM-activated gammadelta T cells, but not that of IPP-activated cells, required cell-to-cell contact. Reciprocally, activation of Vdelta2 T cells by PAM, but not by IPP, was dependent on cell contact with iDCs. In fact, when PAM-stimulated DC-gammadelta T cell cocultures were separated by a semipermeable membrane or treated with blocking anti-CD86 Abs, induction of CD25 and CD69 as well as IFN-gamma and TNF-alpha secretion by Vdelta2 cells were strongly reduced. These results demonstrate for the first time a bidirectional activating interaction between iDCs and PAM-stimulated gammadelta T lymphocytes, thus suggesting a potential adjuvant role of this early cross-talk in the therapeutic activity of aminobiphosphonate drugs.
Conti
Lucia
L
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Casetti
Rita
R
Cardone
Marco
M
Varano
Barbara
B
Martino
Angelo
A
Belardelli
Filippo
F
Poccia
Fabrizio
F
Gessani
Sandra
S
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism; D051940:B7-2 Antigen; D002450:Cell Communication / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004164:Diphosphonates / Q000494:pharmacology*; D045782:Hemiterpenes / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000494:pharmacology; D000077268:Pamidronate; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D004164:Diphosphonates; D045782:Hemiterpenes; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; C004809:isopentenyl pyrophosphate; D007371:Interferon-gamma; D000077268:Pamidronate