In vitro effects of aminobisphosphonates on Vgamma9Vdelta2 T cell activation and differentiation.
In this study we have evaluated the in vitro effects of four different aminobisphosphonates, alendronate, risedronate, neridronate and zoledronate, on Vgamma9Vdelta2 T cell activation and differentiation. All tested aminobisphosphonates induce an IL-2-dependent activation and expansion of Vgamma9Vdelta2 T lymphocytes in primary PBMC cultures of healthy donors. Most notably, they also determine a different distribution of Vgamma9Vdelta2 T cell subsets, with decrease of T(naive) and T(CM) cells and increase of T(EM) and T(EMRA) Vgamma9Vdelta2cells, indicating that in vitro treatment with aminobisphosphonates induces Vgamma9Vdelta2 T lymphocytes to differentiate towards an effector/cytotoxic phenotype. Accordingly, Vgamma9Vdelta2 T lymphocytes cultured with aminobisphosphonates and IL-2 showed a major content of IFN-gamma and acquired the ability to kill tumor target cells.
Ferlazzo
V
V
Dept. of Biopathology and Biomedical Methods, University of Palermo, 90134 Palermo, Italy.
Sferrazza
C
C
Caccamo
N
N
Di Fede
G
G
Di Lorenzo
G
G
D'Asaro
M
M
Meraviglia
S
S
Dieli
F
F
Rini
G
G
Salerno
A
A
D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D019044:Image Cytometry; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007371:Interferon-gamma