FIGURE 8. Linear pyrophosphonates and alkyl-bisphosphonates directly stimulate Vγ2Vδ2 T cells.
A, Direct recognition of HMBPP and HMB-CPCP by Vγ2Vδ2 T cells. Mevastatin and pravastatin inhibition of proliferative and TNF-α responses by the HF.2 Vγ2Vδ2 T cell clone stimulated by 0.1 μM of HMB-OPOP or 316 μM of HMB-CPCP continuously present (top panels) or by 1 μM of HMB-OPOP or 1 mM of risedronate that were pulsed with APC (bottom panels). B, Amino- and alkyl-bisphosphonates stimulate Vγ2Vδ2 T cells. Bisphosphonates were tested for their ability to stimulate TNF-α release by the CD4+ JN.23 Vγ2Vδ2 T cell clone. C, Substitution of an amino moiety for carbon 4 in 1-hydroxy-butane-1,1 bisphosphonate switches direct to indirect stimulation. The CD4+ HF.2 Vγ2Vδ2 T cell clone was continuously stimulated by either n-propyl pyrophosphate (20 μM), 1-hydroxy-butane-1,1 bisphosphonate (20 μM), or 3 amino-1-hydroxy-propane-1,1 bisphosphonate (400 μM) in the presence of mevastatin.