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T Cells: Role of CD86 and Inflammatory Cytokines1
* Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy; and
Laboratory of Advanced Diagnostic and Research, INMI, Rome, Italy
We investigated the interactions between human monocyte-derived dendritic cells (DCs) and Ag-activated circulating TCR-
-expressing lymphocytes (V2). Coculture of immature DCs (iDCs) with peripheral blood V2 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 T cells was mostly mediated by TNF-
and IFN- secreted by activated lymphocytes. However, the effect of PAM-activated T cells, but not that of IPP-activated cells, required cell-to-cell contact. Reciprocally, activation of V2 T cells by PAM, but not by IPP, was dependent on cell contact with iDCs. In fact, when PAM-stimulated DC- 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- and TNF- secretion by V2 cells were strongly reduced. These results demonstrate for the first time a bidirectional activating interaction between iDCs and PAM-stimulated T lymphocytes, thus suggesting a potential adjuvant role of this early cross-talk in the therapeutic activity of aminobiphosphonate drugs.
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