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Copulsing tumor antigen‐pulsed dendritic cells with zoledronate efficiently enhance the expansion of tumor antigen‐specific CD8+ T cells via Vγ9γδ T cell activation
Author(s) -
Takahara Masashi,
Miyai Manami,
Tomiyama Mai,
Mutou Masato,
Nicol Andrew J.,
Nieda Mie
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0307185
Subject(s) - cytotoxic t cell , antigen , biology , cd8 , t cell , tumor antigen , antigen presenting cell , cancer research , immunology , microbiology and biotechnology , in vitro , immune system , biochemistry
We demonstrate that Vγ9γδ T cells activated by zoledronate can link innate and acquired immunity through crosstalk with dendritic cells (DCs) in a way that can amplify activation and proliferation of tumor antigen‐specific CD8+ T cells. DCs pulsed with antigen alone or antigen plus zoledronate were used to stimulate the in vitro expansion of antigen‐specific CD8+ T cells. MART‐1‐modified peptide (A27L peptide) and apoptotic HLA‐A∗0201‐positive, MART‐1‐positive JCOCB tumor cell lines were used as tumor antigen sources. The percentage of A27L‐specific CD8+ T cells within the responding lymphocytes on Day 7 when immature DCs (imDCs) were cultured in the presence of A27L peptide and 0.01 μM zoledronate was significantly higher ( P =0.002, n =11) than that observed when imDCs were cultured with the lymphocytes in the presence of the A27L peptide alone. This enhancing effect of zoledronate was significantly reduced when γδ T cells were depleted from responding lymphocytes ( P =0.030, n =5), indicating that the effect is mediated mainly through Vγ9γδ T cells activated by zoledronate‐pulsed imDCs. When imDCs copulsed with zoledronate and apoptotic JCOCB tumor cell lines were used, the percentage of A27L‐specific CD8+ T cells was higher than that observed using imDCs with the apoptotic JCOCB lines alone, suggesting that zoledronate treatment of imDCs enhances the cross‐presentation ability of DCs. These findings suggest a potentially valuable role for Vγ9γδ T cell activation for expanding antigen‐specific CD8+T cells using DCs copulsed with tumor antigen and zoledronate in the design of vaccine therapies for malignancy.