Activated Vγ9Vδ2 T Cells Trigger Granulocyte Functions via MCP-2 Release
Activated Vγ9Vδ2 T Cells Trigger Granulocyte Functions via MCP-2 Release
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DOI：
10.4049/jimmunol.182.1.522
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发表时间：
2009-01-01
影响因子：
4.4
通讯作者：
Martini, Federico
中科院分区：
文献类型：
--
作者：
Agrati, Chiara;Cimini, Eleonora;Martini, Federico
V γ 9V δ 2 T细胞通过直接杀死感染的细胞和通过诱导有效的适应性免疫应答而显示出广泛的抗微生物活性。氨基二膦酸盐药物如唑来膦酸（ZOL）对V γ 9V δ 2 T细胞的活化导致细胞因子和趋化因子的大量释放，其可诱导其他免疫细胞的旁观者活化。这项工作的目的是评估ZOL激活的V γ 9V δ 2 T细胞释放的可溶性因子诱导粒细胞活化的能力。我们发现，ZOL刺激的V γ 9V δ 2 T细胞释放的可溶性因子通过诱导粒细胞的趋化性、吞噬作用和α-防御素释放来激活粒细胞。蛋白质组学分析使我们能够确定一些细胞因子和趋化因子的活化V γ 9V δ 2 T细胞特异性释放。此外，MCP-2消耗中和抗体揭示了这种趋化因子在诱导粒细胞α-防御素释放的关键作用。总之，这些数据显示了通过旁观者机制的V γ 9V δ 2介导的粒细胞活化，并证实了V γ 9V δ 2 T淋巴细胞在协调免疫应答中的广泛能力。总之，靶向V γ 9V δ 2 T细胞的免疫调节策略可能代表诱导有效和良好协调的免疫应答的关键开关，并且可以被提出作为在感染性疾病期间增强免疫能力的方式。免疫学杂志，2009，182：522-529.
V gamma 9V delta 2 T cells display a broad antimicrobial activity by directly killing infected cells and by inducing an effective adaptive immune response. The activation of V gamma 9V delta 2 T cells by aminobisphosphonate drugs such as zoledronic acid (ZOL) results in a massive release of cytokines and chemokines that may induce a bystander activation of other immune cells. The aim of this work was to evaluate the ability of soluble factors released by ZOL-activated V gamma 9V delta 2 T cells to induce granulocyte activation. We showed that soluble factors released by ZOL-stimulated V gamma 9V delta 2 T cells activate granulocytes by inducing their chemotaxis, phagocytosis, and alpha-defensins release. Proteomic analysis allowed us to identify a number of cytokines and chemokines specifically released by activated V gamma 9V delta 2 T cells. Moreover, MCP-2 depletion by neutralizing Ab revealed a critical role of this chemokine in induction of granulocyte alpha-defensins release. Altogether, these data show a V gamma 9V delta 2-mediated activation of granulocytes through a bystander mechanism, and confirm the wide ability of V gamma 9V delta 2 T-lymphocytes in orchestrating the immune response. In conclusion, an immune modulating strategy targeting V gamma 9V delta 2 T cells may represent a key switch to induce an effective and well-coordinated immune response, and can be proposed as a way to strengthen the immune competence during infectious diseases. The Journal of Immunology, 2009, 182: 522-529.