Potentiation of antigen-stimulated Vγ9Vδ2 T cell cytokine production by immature dendritic cells (DC) and recpirocal effect on DC maturation
Potentiation of antigen-stimulated Vγ9Vδ2 T cell cytokine production by immature dendritic cells (DC) and recpirocal effect on DC maturation
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DOI：
10.4049/jimmunol.176.3.1386
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发表时间：
2006-02-01
影响因子：
4.4
通讯作者：
Scotet, E
中科院分区：
文献类型：
--
作者：
Devilder, MC;Maillet, S;Scotet, E
V γ 9V δ 2 T细胞是成人中主要的γ δ PBL亚群，由于其在外周组织中的高频率和其在识别广泛的保守Ag后产生炎性细胞因子的能力，先前已涉及树突状细胞（DV）许可。尽管这些观察结果暗示V γ 9V δ 2 T细胞对表达Ag的未成熟DC（iDC）的有效识别，但DC亚群在这些淋巴细胞的活化中所起的作用迄今尚未仔细研究。我们表明，MC，并在较小程度上成熟的DC，加强Th 1和Th 2细胞因子，但不是细胞溶解或增殖反应，建立V γ 9V δ 2 T细胞克隆和离体记忆V γ 9V δ 2 PBL刺激的合成激动剂。iDC增强其自身成熟所需的炎性细胞因子的V γ 9V δ 2产生的能力表明，V γ 9V δ 2 T细胞尽管具有强的裂解活性，但可以促进有效的iDC许可，而不会在次优的Ag剂量下杀死。因此，V gamma 9V delta 2细胞诱导表达Ag的iDC加速成熟，但不诱导“旁观者”DC加速成熟，即使在包含表达Ag和不表达Ag的iDC的混合细胞群中也是如此。此外，V γ 9V δ 2细胞诱导被V γ 9V δ 2刺激分枝杆菌感染的iDC完全分化为IL-12产生细胞，否则所述分枝杆菌不能诱导完全DC成熟。总之，iDC选择性增强记忆V γ 9V δ 2 T细胞的细胞因子应答的能力可能是这些淋巴细胞以及可能的其他天然记忆T细胞对常规T细胞应答的佐剂作用的基础。
V gamma 9V delta 2 T cells, a major gamma delta PBL subset in human adults, have been previously implicated in dendritic cell (DV) licensing, owing to their high frequency in peripheral tissues and their ability to produce inflammatory cytokines upon recognition of a broad array of conserved Ags. Although these observations implied efficient recognition of Ag-expressing immature DC (iDC) by V gamma 9V delta 2 T cells, the role played by DC subsets in activation of these lymphocytes has not been carefully studied so far. We show that MC, and to a lesser extent mature DC, potentiated Th1 and Th2 cytokine, but not cytolytic or proliferative responses, of established V gamma 9V delta 2 T cell clones and ex vivo memory V gamma 9V delta 2 PBL stimulated by synthetic agonists. The ability of iDC to potentiate V gamma 9V delta 2 production of inflammatory cytokines required for their own maturation suggested that V gamma 9V delta 2 T cells, despite their strong lytic activity, could promote efficient iDC licensing without killing at suboptimal Ag doses. Accordingly V gamma 9V delta 2 cells induced accelerated maturation of Ag-expressing iDC but not "bystander" DC, even within mixed cell populations comprising both Ag-expressing and nonexpressing iDC. Furthermore V gamma 9V delta 2 cells induced full differentiation into IL-12-producing cells of iDC infected by V gamma 9V delta 2-stimulating mycobacteria that were otherwise unable to induce complete DC maturation. In conclusion the ability of iDC to selectively potentiate cytokine response of memory V gamma 9V delta 2 T cells could underlie the adjuvant effect of these lymphocytes, and possibly other natural memory T cells, on conventional T cell responses.