In vitro effects of aminobisphosphonates on Vγ9Vδ2 T cell activation and differentiation

被引:23
作者
Ferlazzo, V.
Sferrazza, C.
Caccamo, N.
Di Fede, G.
Di Lorenzo, G.
D'Asaro, M.
Meraviglia, S.
Dieli, F.
Rini, G.
Salerno, A.
机构
[1] Univ Palermo, Dipartimento Biopatol & Metodol Biomed, I-90134 Palermo, Italy
[2] Univ Palermo, Dipartimento Med Clin & Malattie Emergenti, I-90134 Palermo, Italy
[3] CNR, Ist Biomed & Immunol Mol, I-90146 Palermo, Italy
关键词
V gamma 9V delta 2 T cells; aminobisphosphonates; cytoloxicity; memory cells; effector cells;
D O I
10.1177/039463200601900208
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In this study we have evaluated the in vitro effects of four different aminobisphosphonates, alendronate, risedronate, neridronate and zoledronate, on V gamma 9V delta 2 T cell activation and differentiation. All tested aminobisphosphonates induce an IL-2-dependent activation and expansion of V gamma V delta 2 T lymphocytes in primary PBMC cultures of healthy donors. Most notably, they also determine a different distribution of V gamma 9V delta 2 T cell subsets, with decrease of T-naive and T-CM cells and increase of T-EM and T-EMRA V gamma 9V delta 2 cells, indicating that in vitro treatment with ammobisphosphonates induces V gamma 9V delta 2 T lymphocytes to differentiate towards an effector/cytotoxic phenotype. Accordingly, V gamma 9V delta 2 T lymphocytes cultured with aminobisphosphonates and IL-2 showed a major content of IFN-gamma and acquired the ability to kill tumor target cells.
引用
收藏
页码:309 / 317
页数:9
相关论文
共 48 条
[1]  
Amin D, 1996, ARZNEIMITTEL-FORSCH, V46, P759
[2]  
AMIN D, 1992, J LIPID RES, V33, P1657
[3]   Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase [J].
Bergstrom, JD ;
Bostedor, RG ;
Masarachia, PJ ;
Reszka, AA ;
Rodan, G .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2000, 373 (01) :231-241
[4]   ISOPRENOID (PHOSPHINYLMETHYL)PHOSPHONATES AS INHIBITORS OF SQUALENE SYNTHETASE [J].
BILLER, SA ;
FORSTER, C ;
GORDON, EM ;
HARRITY, T ;
SCOTT, WA ;
CIOSEK, CP .
JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (10) :1869-1871
[5]   Differential requirements for antigen or homeostatic cytokines for proliferation and differentiation of human Vγ9Vδ2 naive, memory and effector T cell subsets [J].
Caccamo, N ;
Meraviglia, S ;
Ferlazzo, V ;
Angelini, D ;
Borsellino, G ;
Poccia, F ;
Battistini, L ;
Dieli, F ;
Salerno, A .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2005, 35 (06) :1764-1772
[6]  
CIOSEK CP, 1993, J BIOL CHEM, V268, P24832
[7]   Integrin-mediated signals regulated by members of the Rho family of GTPases [J].
Clark, EA ;
King, WG ;
Brugge, JS ;
Symons, M ;
Hynes, RO .
JOURNAL OF CELL BIOLOGY, 1998, 142 (02) :573-586
[8]   Identification of a novel phosphonocarboxylate inhibitor of Rab geranylgeranyl transferase that specifically prevents Rab prenylation in osteoclasts and macrophages [J].
Coxon, FP ;
Helfrich, MH ;
Larijani, B ;
Muzylak, M ;
Dunford, JE ;
Marshall, D ;
McKinnon, AD ;
Nesbitt, SA ;
Horton, MA ;
Seabra, MC ;
Ebetino, FH ;
Rogers, MJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (51) :48213-48222
[9]   The bisphosphonate tiludronate is a potent inhibitor of the osteoclast vacuolar H+-ATPase [J].
David, P ;
Nguyen, H ;
Barbier, A ;
Baron, R .
JOURNAL OF BONE AND MINERAL RESEARCH, 1996, 11 (10) :1498-1507
[10]  
Dieli F, 2000, EUR J IMMUNOL, V30, P1512, DOI 10.1002/(SICI)1521-4141(200005)30:5<1512::AID-IMMU1512>3.0.CO